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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 32 (1989), S. 271-281 
    ISSN: 1432-0428
    Keywords: Insulin ; granule ; vesicle ; proton pump ; prohormone conversion ; autocrine ; chromogranin A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The insulin secretory granule of the pancreatic B cell is a complex intracellular organelle comprised of a many proteins with different catalytic activities and messenger functions. With the advent of tumour models of the B cells and the application of immunological and molecular cloning techniques considerable progress has been made in recent years towards the elucidation of the structure and function of these granule proteins. A number of examples are selected here for review. Particular emphasis given to how the activities of quite different granule proteins are interdependent and how this contributes to the co-ordination and integration of the organelle's biological functions.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: C-peptide ; Insulin ; Pancreaticβ cells ; Insulinoma morphometry ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been shown, by using the immunogold technique, that C-peptide and insulin are co-localized in the mature granules of human pancreaticβ cells and insulinomas with typical granules. The mean gold bead densities of both C-peptide and insulin were at least twice as high in the normal pancreas when compared with the insulinomas. The mean granule diameter of the insulinoma cells (D=0.30 ±0.12 μm) was smaller than that of human pancreatic cells (D=0.45 ±0.15 μm). The morphometric data indicate that each of the antigens (C-peptide and insulin) is distributed similarly in the halos and the dense cores of theβ granules. Thus, no topological segregation of these two antigens occurs within theβ granules of either normal human pancreas or insulinomas.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin ; des-(B26-B30)-insulinamide ; [TyrB25]des-(B26-B30)insulinamide ; [HisB25]des-(B26-B30)-insulinamide ; liver metabolism ; rat hepatocyte culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Short-term and long-term biological activities were studied in adult rat hepatocytes cultured in the presence of the insulin analogues des-(B26-B30)-insulinamide, [TyrB25]des-(B26-B30)-insulinamide and [HisB25]des-(B26-B30)-insulinamide. When compared to insulin, full potency of des-(B26-B30)-insulinamide has been reported in rat adipocytes and an enhanced potency has been reported for the other analogues. Steady state binding characteristics of the analogues to hepatocytes were indistinguishable from those of native insulin with half-maximal binding occurring at concentrations of about 0.8 nmol/l. Half-maximal effects for the stimulation of glycolysis and inhibition of basal and glucagon-activated glycogenolysis required identical concentrations for insulin and all 3 analogues. Induction of the key glycolytic enzymes glucokinase and pyruvate kinase as well as the inhibition of glucagon-dependent induction of phosphenolpyruvate carboxykinase also required identical concentrations of insulin and the 3 analogues. These data confirm that in cultured hepatocytes the C-terminal amidation of des-(B26-B30)-insulin results in a molecule with full in vitro potency. In contrast to data obtained in adipocytes, the des-(B26-B30)-insulin-amidated analogues with tyrosine or histidine substitutions at position B25 are equally as potent as native insulin in eliciting biological responses in rat hepatocyte culture.
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  • 4
    ISSN: 1432-1440
    Keywords: Human thyroid cells ; Thyroid cell growth ; bTSH ; Insulin ; Insulin-like growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of TSH in thyroid cell growth and the pathogenesis of goiter has become a matter of recent debate, since many investigators have failed to demonstrate a growth-promoting effect of TSH in human thyroid cells in culture. While those studies have focused on the action of TSH in human thyroid cells, the influence of assay conditions and cofactors has received scant attention. In the present study, we have therefore undertaken to elucidate the effects of insulin and insulin-like growth factor (IGF I) on3H-thymidine uptake in human thyroid cells, particularly with respect to their relation to the actions of bTSH. We could demonstrate a considerable, dose-dependent stimulation of3H-thymidine incorporation in the cells by bTSH that was dependent on the presence of insulin or IGF I; bTSH alone was ineffective in that respect. The concentrations of insulin and IGF I required to facilitate the TSH response were of a magnitude at which both peptides were totally ineffective by themselves. At concentrations of insulin or IGF I that produced a maximum stimulation of3H-thymidine incorporation, the addition of bTSH did result in a slight decrease rather than a further increase of that stimulation. We conclude from these findings, first, that TSH appears to be a growth factor for human thyroid cells under the conditions described, and, second, the effects of TSH on thyroid cell proliferation are under the control of cofactors like insulin and IGF I.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 11 (1989), S. 236-243 
    ISSN: 1573-739X
    Keywords: Absorption ; Diabetes mellitus, insulin-dependent ; Injections, subcutaneous ; Insulin ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0878
    Keywords: Islet amyloid peptide ; Pancreatic islets ; Type-2 diabetes ; Insulin ; Lysosomes ; Secretory granules ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Islet amyloid peptide (or diabetes-associated peptide), the major component of pancreatic islet amyloid found in type-2 diabetes, has been identified by electronmicroscopic immunocytochemistry in pancreatic B-cells from five non-diabetic human subjects, and in islets from five type-2 diabetic patients. The greatest density of immunoreactivity for islet amyloid peptide was found in electrondense regions of some lysosomal or lipofuscin bodies. The peptide was also localised by quantification of immunogold in the secretory granules of B-cells, and was present in cytoplasmic lamellar bodies. Acid phosphatase activity was also demonstrated in these organelles. Immunoreactivity for insulin was found in some lysosomes. These results suggest that islet amyloid peptide is a constituent of normal pancreatic B-cells, and accumulates in lipofuscin bodies where it is presumably partially degraded. In islets from type-2 diabetic subjects, amyloid fibrils and lipofuscin bodies in B-cells showed immunoreactivity for the amyloid peptide. Abnormal processing of the peptide within B-cells could lead to the formation of islet amyloid in type-2 diabetes.
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  • 7
    ISSN: 1432-0878
    Keywords: Gut hormones ; Insulin ; Bombesin ; Immunocytochemistry ; Pancreatic polypeptide ; Cholecystokinin (CCK) ; Gastrin ; Schistocerca gregaria (Insecta)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The endocrine cells of the midgut epithelium of the desert locust are found dispersed among the digestive cells and are similar to those of the vertebrate gut. According to their reactivity to silver impregnation techniques and the ultrastructural features of the secretory granules (shape, electron-density, size, and structure) 10 types of endocrine cell have been identified, of which seven are located in the main segment of the midgut or in the enteric caeca, and the other three seem to be present only in the ampullae through which the Malpighian tubules drain into the gut. The endocrine cells have a slender cytoplasmic process that reaches the gut lumen, a feature that supports the receptosecretory nature postulated for this cellular type in insects as well as vertebrates. Antisera directed against mammalian gastrin, CCK, insulin, pancreatic polypeptide and bombesin reacted with some of the endocrine cells. This is the first time that insulin- and bombesin-like immunoreactive cells have been described in the midgut of an insect.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 1 (1989), S. 122-128 
    ISSN: 1040-452X
    Keywords: Pachytene spermatocytes ; Round spermatids ; Insulin ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: In vitro rat germ cell RNA synthesis is influenced by growth factors. Basic fibroblast growth factor (0.1 to 100 ng/ml) increases [3H]uridine incorporation in round spermatids (RS) but not in pachytene spermatocytes (PS); this effect is potentiated by insulin (10 μg/ml) and blocked in the presence of Sertoli cell-secreted proteins (SCSP). Somatomedin C (0.1 to 100 ng/ml) exhibits a similar effect when used alone without an influence by SCSP. Transforming growth factor β (0.1 to 10 ng/ml) acts on both cell types, but SCSP amplify this effect only in PS. These data suggest that growth factors synthesized in situ may play a role in the germ cell development and that their effects are moduiated by SCSP.
    Additional Material: 6 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    Hoboken, NJ [u.a.] : Wiley-Blackwell
    Journal of Orthopaedic Research 7 (1989), S. 35-42 
    ISSN: 0736-0266
    Keywords: Articular cartilage ; Somatomedin ; Growth factors ; Insulin ; Culture ; Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We have examined the effect of peptide growth factors on DNA and proteoglycan synthesis by adult bovine articular cartilage in organ culture. The actions of somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I), insulin, epidermal growth factor (EGF), and fibroblast growth factor (FGF) from bovine pituitary were investigated individually and in combination. FGF stimulated a 10-fold increase in tritiated thymidine incorporation while other factors used individually did not influence mitotic activity. Used in concert, insulin with EGF and insulin with FGF acted synergistically in stimulating DNA synthesis 20-fold and 40-fold, respectively. All of these growth factors, acting individually, significantly enhanced radiosulfate incorporation. This stimulation was additive for Sm-C/IGF-I in combination with EGF or FGF, but not with insulin. These data indicate that adult bovine articular chondrocytes possess the capacity to augment both mitotic and differentiated cell functions in response to growth factors. The data further suggest that, with the exception of insulin and Sm-C/IGF-I, which appear to share a common mechanism of action, these factors produce their cellular effects via different receptor or postreceptor pathways.
    Additional Material: 8 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 44 (1988), S. 1-9 
    ISSN: 1420-9071
    Keywords: Insulin ; glucagon ; pancreatic polypeptide ; somatostatin ; fetal pancreas ; ontogeny ; immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ontogeny of insulin, glucagon, PP and somatostatin in the mammalian fetal pancreas has been examined in recent years largely by immunocytochemistry and in some instances by radioimmunoassay. Complete ontogenic data are available only for the rat, human pig and sheep. Figure 3 compares the time of appearance of the endocrine cell-types within the fetal pancreas when the periods of gestation of the four species are converted to a uniform scale. The striking ontogenic difference in the rat probably reflects the immaturity of the rodent fetus at birth compared with the human, pig and sheep. In the fetal pancreas, differences in cell number of glucagon and PP cells in the dorsal and ventral lobes become apparent from an early gestational period. Factors responsible for the functional and structural maturation of the fetal pancreatic endocrine cells and the processes involved in pancreatic organogenesis are poorly understood. Studies in these areas would have clinical implications since it may be possible in the future to employ agents for selective replication of fetal β-cells for transplantation in patients with Type I diabetes, bearing in mind that such cells must have the capacity to respond to normal stimuli and repressors when transplanted. The presence of the other islet cell-types may be obligatory for these appropriate responses. This would require a more complete knowledge of those factors which produce the normal selectivity of the four hormonal cell-types.
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  • 11
    ISSN: 1432-0568
    Keywords: Pancreatic islet ; Insulin ; Glucagon ; Ontogeny ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ontogenetic appearances of glucagon, insulin and tyrosine hydroxylase (TH) were immunohistochemically investigated on developing pancreatic islets of rats. Glucagon immunoreactivity appeared first in some epithelial cells (g-cells) of the dorsal anlage of the pancreas on day 11.5 of gestation. On day 12.5, g-cells increased in number manufacturing the primitive islets, in which some cells appeared to be immunoreactive for insulin (i-cells) and about 40% of g-cells indicated also a slight immunoreactivity for insulin (g/i-cells). Afterwards, all the islet cells, especially g-cells, increased in number, and almost half of g-cells were g/i-cells. After day 16.5 of gestation, numerical increase of the cells with insulin immunoreactivity exceeded that of the cells with glucagon immunoreactivity, and about one fifth of g-cells were g/i-cells. After 20.5 days, however, no g/i cells were found. On day 16.5 of gestation, the immunoreactivity for TH appeared in occasional cells of the islets, but the cells did not show immunoreactivity for glucagon or insulin. It is concluded that the progenitor cells of the pancreatic islets appear to synthesize both glucagon and insulin by day 20.5 of gestation, but differentiate giving rise to mature A and B cells of adult isoets afterward.
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  • 12
    ISSN: 1432-1440
    Keywords: Growth hormone-Releasing hormone ; Somatostatin ; Insulin ; Type 1 diabetic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following a mixed meal, plasma hormone responses were measured in four type 1 diabetic children and in eight short normal children. Between 60 and 150 min after ingestion of the mixed meal there was a significant increase in circulating growth hormone-releasing hormone values both in diabetic and in normal children. Mean plasma GHRH peak values were not different between diabetic patients (27.0±3.9 ng/l) and controls (24.6±4.9 ng/l). No time relationship to spontaneous growth hormone peaks was observed. Whereas normal children showed a characteristic biphasic plasma somatostatin response, somatostatin plasma levels in diabetic children did not change. In normal children plasma insulin values increased between 30 and 150 min, but remained unchanged in type 1 diabetic patients. Blood glucose response was more pronounced in diabetic children than in short normal children. These results indicate that circulating growth hormone-releasing hormone does not play a dominant role in the regulation of insulin and somatostatin.
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  • 13
    ISSN: 1432-2307
    Keywords: AVP/SV40 transgenic mice ; Immunocytochemistry ; Insulin ; Pancreatic polypeptide ; Large T-antigen ; Heterochromatin ; Dysplasia ; Neoplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insertion into the mouse genome of the hybrid oncogene made up of bovine vasopressin gene derived 5′ upstream sequences and the coding sequences of SV40 large T-antigen promoted tumours in anterior pituitary and endocrine pancreas of mice bearing this transgene. In order to investigate the morphology of the steps in the neoplastic process, we used light and electron microscopy to study these organs in 42 animals belonging to the 3rd, 4th and 5th generations, subdivided into 4 age groups from 20 days to 100 days of life. Antibodies to large T-antigen were used to identify sites of expression of the hybrid oncogene, thus monitoring the steps in neoplastic transformation. Large T-antigen immunoreactivity was identified in dysplastic lesions of younger animals and in both dysplastic lesions and tumours of older mice. Insulin (100% of cases) and pancreatic polypeptide (25% of cases) immunoreactivities were revealed in pancreatic lesions but no hormonal immunoreactivity was detected in the pituitary lesions. The ultrastructural study confirmed that the majority cell population of the pancreatic neoplasms was B-type and that the anterior pituitary tumours were poorly granulated. The subcellular localization of large T-antigen immunoreactivity was investigated by the immunogold method and was confined to the heterochromatin of tumour cell nuclei. These findings provide evidence for the dysplasia-neoplasia sequence in the genesis of endocrine tumours of pituitary and pancreas of transgenic mice. The vasopressin-SV40 large T-antigen transgenic mice may therefore be an useful model for the study of endocrine cell oncogenesis,
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  • 14
    ISSN: 1432-2307
    Keywords: Insulin ; Insulinomas ; Ultrastructure ; Immunogold technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Localisation of insulin-like immunoreactivity has been studied using the immunogold staining procedure on thin sections of 6 human insulinomas, conventionally processed for electron microscopy. The labelling was restricted to the secretory granules. Depending on their morphology, these either resembled B-cell granules of human adult pancreas or belonged to the atypical (non-diagnostic) group. Within the former group, those with a crystalloid core or an amorphous dense or moderately dense core were strongly immunoreactive, whereas others, filled with a pale material, were poorly labelled. Most granules of this type were stored together within the heavily granulated cells of 3 insulinomas, presenting the classical features of clinical and biological behaviour and a typical light microscopic staining pattern. In contrast, the non-diagnostic granules, characterized by their smaller size, a very dense core and a thin halo, were mainly found within the poorly granulated cells making up the other tumours, and showed a very uneven labelling. Strongly labelled granules were found in one insulinoma that also belonged to the classical type; these were stored together with a few diagnostic granules within the same cells. Only poorly labelled atypical granules were present in two cases revealing a number of unusual features; these included moderate elevation of insulinaemia, uncertain tumour histology, as well as weak immunostaining for insulin/proinsulin and variable argyrophilia of the tumour in paraffin sections. These findings suggest that human insulinomas differ not only in storage capacity but also in their degree of granule maturation. This may involve some deficiency of either the prohormone conversion or the subsequent processing of the cleavage products.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 13 (1988), S. 1119-1124 
    ISSN: 1573-6903
    Keywords: Insulin ; astroglia ; cultures ; GABA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Astroglial cultures from newborn mouse cerebral cortex contain [125I]insulin binding sites. Binding was specific reversible, time dependent and reached equilibrium after 45 min. Insulin analogues compete for this [125I]Insulin binding. Incubation of cerebral cortex astroglial cultures with insulin induced a time-and dose-dependent inhibition of the [3H]GABA high affinity uptake. A decrease in theV max rather than, an effect on theK m was observed. This effect was dose-dependent and effective at 10−10 M. Autoradiographic observations on the cell monolayer showed the presence of two groups of cells: one which strongly takes up [3H]GABA and consist in smaller GFAP positive process-bearing cells and another group of much flatter and larger GFAP positive cells which uptake was lower. The smaller stellate cells were apparently the most sensitive to insulin effect. These results: 1) confirm the presence of insulin binding sites on astroglial primary cultures, 2) show an effect of insulin of [3H]GABA high affinity uptake of these cells; this effect being optimal on a stellate-like population of astrocytes, and 3) indicate, that insulin may interfere in neuromodulation through astroglial signals.
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  • 16
    ISSN: 1573-6903
    Keywords: Insulin ; receptors ; brain ; cultures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The presence and specificity of insulin receptors was investigated in cultured cells obtained from 15–16 days old embryonic mouse cerebra. Developmental studies suggested that the maximum insulin binding occurred at about 11 days in vitro (DIV). Scatchard analysis of binding data revealed two types of binding sites. One type of receptor was the high affinity type (K d=7.77×10−9 M; number of receptor sites,B max=350 fmol/mg protein) while the other type was of low affinity type (K d=5.75×10−8 M;B max=1150 fmol/mg protein). The specificity of receptors for insulin was also confirmed by showing that [125I]insulin was displaced by non-radioactive insulin but not by glucagon or growth hormone. Insulin displayed a clear dose-dependent stimulation of thymidine incorporation. It also stimulated the activity of the enzyme 2′,3′-cyclic nucleotide phosphohydrolase (CNPase), which is specifically associated with myelin produced from oligodendroglia. Thus insulin has a positive influence on the proliferation and differentiation of brain cells.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 13 (1988), S. 887-892 
    ISSN: 1573-6903
    Keywords: Insulin ; streptozotocin ; diabetes ; noradrenaline ; dopamine ; p-tyrosine ; hypothalamus ; olfactory tubercles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A single intracardial injection of streptozotocin produced a significant increase in rat hypothalamic noradrenaline while no changes were observed in the olfactory tubercles. The parenteral administration of a single dose of insulin decreased rat hypothalamic noradrenaline; the effect had a rapid onset and lasted for at least six hours. Similar noradrenaline reductions were observed in the olfactory tubercles but in this tissue the depletion started later and recovered earlier. In addition, in olfactory tubercles after insulin injection, tyrosine level and dopamine metabolism were increased. The results show that the increases in hypothalamic NA observed in streptozotocin diabetic rats are counteracted by insulin administration and possibly the consequence of changes in noradrenaline turnover.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 31 (1988), S. 51-53 
    ISSN: 1432-0428
    Keywords: Insulin ; erythrocyte ; diabetes ; glucose metabolism ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alloxan-induced diabetes in rats significantly impaired the capacity of the erythrocytes to metabolise glucose in vitro to either lactic acid or CO2. Both these metabolic activities were initially insensitive to insulin in normal as well as in diabetic animals; but became responsive when these cells were subjected to insulin and glucose ‘starvation’ for 1 h through incubation in their absence. This action of insulin in starved cells showed concentration dependence and required preincubation with the hormone prior to addition of glucose.
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  • 19
    ISSN: 1432-0428
    Keywords: Insulin ; glucose ; age ; children ; puberty
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pattern of insulin secretion was studied in 107 normal individuals aged 5 to 50 years. Intravenous glucose tolerance tests were performed on 64 islet-cell antibody negative siblings of diabetic children and on 43 normal adults. Puberty was staged using Tanner's criteria and subjects were grouped as follows: I — stage 1 (n=22), II — stages 2 and 3 (n=18), III — stages 4 and 5 (n=20), IV — adults 〉17 years (n=47). Basal and stimulated (incremental 0–10 and 10–60 min areas) insulin responses rose throughout puberty (Groups I–III), declined following puberty until the third decade (Groups III and IV) and then appeared constant thereafter. Insulin levels in the 17.6–22.5 year group were lower than in the 12.6–15 year group (p〈0.01). Fasting insulin to glucose ratios and incremental 0–60 min insulin to glucose area ratios produced a similar age-related pattern indicating that changes in insulin levels were independent of glucose concentrations. Gender did not affect these changes and multiple regression analysis showed that HLA haplotype sharing did not influence insulin responses in siblings of diabetic patients. Age and pubertal status must be carefully considered when interpreting intravenous glucose tolerance tests from patients suspected of having early abnormalities of carbohydrate metabolism.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 412 (1988), S. 258-263 
    ISSN: 1432-2013
    Keywords: Acetylcholine ; Quanta ; Na+−K+ exchange pump ; Ouabain ; Adrenaline ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment with hypertonic solutions, insulin, or adrenaline increases the size of quanta at the frog neuromuscular junction, as determined by measurements of miniature end plate potentials or currents (Van der Kloot and Van der Kloot 1985, 1986). The increase in quantal size apparently is due to an increase in acetylcholine (ACh) content of individual quanta. These treatments, therefore, can be used to study the packaging of ACh. Previously, I reported that increases are blocked by an inhibitor of active ACh uptake into vesicles (Van der Kloot 1986b, 1987b). The present study shows that the increases in quantal size were antagonized by inhibiting the Na+−K+ exchange pump with 100 μM ouabain, 10 μM dihydroouabain, or K+-free solutions. The increases in quantal size were also antagonized by 10 μM monensin, a Na+ ionophore, or by 5 μM aconitine, which opens Na+ channels at normal resting potentials. Apparently a rise in intracellular [Na+] inhibits the addition of ACh to quanta. The mechanism by which a rise in intracellular Na+ inhibits ACh packing is unknown, but apparently it is not due to inhibition of choline reuptake into the terminals. Also consistent with the above hypothesis is that the increase in quantal size following depolarization for 2 h in elevated [K+]out was substantially enhanced when tetrodotoxin (TTX) was present, suggesting that in the absence of TTX there is a rise in [Na+]in that antagonizes the incorporation of additional ACh into the quanta.
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  • 21
    ISSN: 1432-2013
    Keywords: Nephron microdissection ; Glomeruli ; Tubules ; [125I] Insulin binding ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Binding of [125I] Tyr A14 human insulin ([125I] insulin) was measured at 4°C in glomeruli and pieces of tubule microdissected from collagenase-treated rat kidneys. For glomeruli and all segments tested, total and non specific binding increased linearly with glomeruli number or tubular length. When determined with 4.0 nM labelled hormone, the distribution of specific binding sites (expressed as 10−18 mol [125I] insulin bound per glomerulus or mm tubule length) was as follows: glomerulus, 2.5±0.3; proximal convoluted tubule (PCT), 12.6±0.6; pars recta (PR), 4.0±2.3; thin descending limb (TDL), 0.6±0.2; thin ascending limb (TAL), 0.6±0.2; medullary thick ascending limb (MAL), 0.8±0.1; cortical ascending limb (CAL), 2.1±0.1; distal convoluted tubule (DCT), 5.6±1.1; cortical collecting tubule (CCT), 3.2±0.3 and outer medullary collecting tubule (MCT), 2.3±0.1. Specific [125I] insulin binding to glomeruli and tubule segments was time- and dose-dependent, saturable, reversible after elimination of free labelled ligand, and inhibited by unlabelled human insulin. When analysed in Scatchard and Hill coordinates, the binding data revealed a negative cooperation in the interaction processes between [125I] insulin and glomerular and tubular binding sites, with apparent dissociation constants and Hill coefficients of the following values: glomerulus, 0.6 nM and 0.60; PCT, 10.0 nM and 0.55; MAL, 4.3 nM and 0.80; CAL, 2.0 nM and 0.74; CCT, 7.6 nM and 0.80 and MCT, 1.0 nM and 0.57 respectively. The stereospecificity of nephron binding sites was assessed in competitive experiments showing that unlabelled bovine and procine insulins were as efficient as human insulin for displacing [125I] insulin, whereas A and B chains of insulin and unrelated peptide hormones were almost inactive. These results indicate that the detected [125I] insulin binding sites may correspond to physiological insulin receptors.
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 66 (1988), S. 924-927 
    ISSN: 1432-1440
    Keywords: Hypertension ; Insulin ; Glucagon ; Skeletal muscle ; Glycogen ; Glucose ; Glycogen synthetase ; Glycogen phosphorylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was performed to investigate as to whether peripheral insulin resistance exists in spontaneously hypertensive rats (SHR). After a 12 h fasting period, SHR had significantly higher serum glucose and higher plasma glucagon values in comparison to normotensive control rats (WKY). There was a tendency for higher serum insulin concentrations as well, but this difference did not reach significance. After oral glucose loading or glucose/insulin administration, serum glucose and insulin levels were also higher in SHR compared to WKY rats. Muscle glycogen and glucose concentrations were identical in fasted SHR and WKY rats. With an oral glucose load or glucose/insulin treatment there was a significant increase in muscle glycogen, whereas glucose values declined in skeletal muscle. Both total (a+b-form) phosphorylase activity as well as the active a-form of the enzyme were similar in skeletal muscle of SHR and WKY rats. Glucose/insulin administration or oral glucose loading induced a considerable reduction of both a+b-form and a-form activities. The decrease in muscle phosphorylase activities was almost identical in both groups of animals. There was also a comparable activity of muscle glycogen synthetase activity in all groups of rats. Despite subtile changes of glucose, glucagon and to a lesser degree insulin levels which would be suggestive of insulin resistance, the data obtained from skeletal muscle argue against peripheral insulin resistance in spontaneously hypertensive rats.
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  • 23
    ISSN: 1432-0428
    Keywords: Insulin ; glucagon ; thyroid hormones ; glucose turnover ; glucose production ; glucose utilisation ; glucoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The glucoregulatory function of glucagon was investigated in hypo-, eu- and hyperthyroid miniature pigs. Infusion glucagon, (3 ng x kg body weight−1 · min−1) transiently increased blood glucose (p〈0.01) and hepatic glucose production (p〈0.01) in euthyroidism, but was without effect in hyperthyroidism. Infusing glucagon plus somatostatin (2 ng x kg body weight−1 · min−1 and 0.2 μg x kg body weight−1 · min−1) transiently increased blood glucose (Δ 3.0 to 4.3 mmol/l) and hepatic glucose production (Δ 3.3 to 7.7 umol x kg body weight−1 · min−1) in all thyroid states, the effect was less pronounced in hyperthyroid pigs. By contrast, hypoglucagonaemia (74 to 107 pg/ml) at basal insulin (28 to 35 μU/ml) provoked hypoglycaemia (1.4 to 2.2 mmol/l) and a fall in glucose production (Δ 4.7 to 8.3 umol x kg body weight−1 · min−1), which was independent of the thyroid state; the effect was most pronounced in hyperthyroidism (p〈0.01). Hepatic glycogen content, arterial gluconeogenic precursor concentrations as well as the glycaemic response (Δ 0.60 mmol/l) to alanine infusion (23 umol x kg body weight−1 · min−1) were all unaffected by hyperthyroidism. We conclude that moderate experimental hyperthyroidism reduces glucagon action due to reduced glycogen mobilisation. This may in part result from increased insulin sensitivity.
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  • 24
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    Research in experimental medicine 188 (1988), S. 27-33 
    ISSN: 1433-8580
    Keywords: Carbon tetrachloride ; Insulin ; Glucagon ; Cytochrome P450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats given a dose of carbon tetrachloride (CCl4) immediately received injections of glucagon and insulin every 4h. They frequently died after 4h and showed a significantly higher mortality between 8h and 28h as compared to the control rats where such deaths occurred 16h later. At 8h, the derangements of SGPT values and prothrombin time were significantly greater in the hormone-treated rats than in the control rats. In these CCl4-intoxicated rats, hepatic reduced glutathione content at 4h was significantly reduced after hormone treatment. The treatment significantly enhanced CCl4 metabolism, conversion of14CCl4 into14CO2 in vitro, by microsomes isolated from the liver, whereas it did not affect the microsomal cytochrome P450 content. These results suggest that glucagon and insulin treatment increased CCl4 hepatotoxicity in rats through activating the cytochrome P450-dependent mono-oxygenase system. This would merit consideration for the clinical application of this treatment.
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  • 25
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    Pharmacy world & science 10 (1988), S. 213-216 
    ISSN: 1573-739X
    Keywords: Adsorption ; Equipment and supplies ; Infusions, parenteral ; Insulin ; Polyethylenes ; Polyvinylchloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A comparison between human and porcine insulins with regard to their adsorption to administration sets was performed. A125I-mono(A14)-iodinated insulin was used to follow the adsorption phenomenon over time and the adsorption was quantified with radioimmunoassays of unlabelled insulin. The obtained data were similar for both methods. No relevant difference in adsorption was found between human and porcine insulin. Both insulins showed a significantly more pronounced initial drop in delivered insulin when polyethylene tubing was used. After 3 h a steady state was reached, resulting in the administration of a more predictable dose. Particularly in the initial phase an important reduction in the amount of both insulins actually delivered to the patient was observed when compared to the expected amount as calculated from the concentration present in the container and the infusion rate. Therefore, the mainstay in treatment of a patient with ketoacidosis remains frequent serum glucose measurement and making appropriate infusion rate adjustments on that basis.
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  • 26
    ISSN: 1573-739X
    Keywords: Absorption, transdermal ; Brilliant Blue ; Dodecyl-l-pyroglutamate ; Insulin ; Laurocapram ; N-Methyl-2-pyrrolidone ; Permeability, enhancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The study reports on penetration enhancers used to improve drug absorption through the skin. All experiments were carried out in permeation cellsin vitro. Insulin (2.5 mg/ml) and Brilliant Blue (50.0 mg/ml) served as model drugs. They were formulated into a 40% solution of propylene glycol with increasing concentrations ofN-methyl-2-pyrrolidone (NMP) (0.0 to 20.0%), dodecylazacycloheptan-2-one (laurocapram) and a new compound dodecyl-l-pyroglutamate (DLP; 0.0 to 0.5%). The maximum amount of insulin permeated within 24 h was almost 200 μU/ml in the case of 0.1% laurocapram, while in the case of 0.1% DLP it was approximately half of that. The optimum concentration of NMP was 12.0%. Experiments performed with Brilliant Blue showed no significant difference among formulations containing either 6.0, 12.0 or 20.0% of NMP. When NMP was omitted, flux, permeability as well as the maximum concentration estimated after 26 h reached 50% of the values obtained with NMP. The lag time was twice as long in this case in comparison with the formulations containing NMP.
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  • 27
    ISSN: 1439-6327
    Keywords: Glucose and fat feeding ; Glycogen sparing ; Ketone bodies ; Insulin ; Lipolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to test the hypothesis that oral ingestion of lipids could increase endurance by slowing the rate of glycogen depletion. Trained rats were killed after a 2 h run on a rodent treadmill, following an intragastric infusion of water, glucose, medium chain triglycerides (MCT) or long chain triglycerides (LCT). Glucose and triglycerides were administered in equicaloric concentrations (50 kJ). The results show that oral ingestion of lipids (MCT or LCT) did not reduce glycogen depletion in liver, heart or skeletal muscle after exercise whereas the fat diet increased muscle and heart glycogen stores in resting conditions. In contrast, glucose feeding induced a significant sparing effect on endogenous carbohydrate utilization and reduced physical exercise lipolysis. These data indicated, firstly, that enhanced lipid availability induced by a single lipid meal before exercise was not able to modify the glycogen depletion occuring after exercise and, secondly, that the glucose/fatty acid cycle was not effective in these conditions. The comparison between lipids indicated that the effect on glycogen use of MCT did not differ from that of LCT, and did not seem to be of any particular importance during physical exercise.
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  • 28
    ISSN: 1439-6327
    Keywords: Energy metabolism ; Carbohydrate-rich diet ; Lipoprotein lipase ; Free fatty acids ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparison of the influence of simple and complex carbohydrate (CHO) consumption on adipose tissue- and skeletal muscle-lipoprotein lipase activity (AT-LPLA, SM-LPLA) was examined. Twenty male marathon runners were divided into two equal dietary groups: simple-CHO and complex-CHO. Half of the subjects in each group consumed either a low-CHO (15% energy [E] intake), or a mixed diet (50% CHO) for 3 days. Immediately following this dietary period, the subjects consumed a CHO-rich diet (70% E intake) predominant in simple-CHO or in complex-CHO for an additional 3 days. Thereafter, all subjects returned to a normal mixed diet. Skeletal muscle biopsies, adipose tissue aspirations, and venous blood samples were obtained prior to dietary manipulation (PRE), upon completion of the 6 day diet (POST I), and 2 weeks after returning to a normal diet (POST II). The samples were analysed for AT-LPLA, SM-LPLA, serum insulin, and free fatty acids (FFA), and blood glucose, and lactate. SM-LPLA fell 71% from PRE values of 0.39±0.30 μ mol · g−1 · h−1 to POST I values of 0.11 ±0.09 μ mol · g−1 · h−1 (means±SD) (p〈0.05), after a complex-CHO diet. However, the simple-CHO diet did not alter SM-LPLA. AT-LPLA similarly decreased (p〈0.05) after the complex-CHO diet, and no significant decrease was noted after the simple-CHO diet. Serum FFA decreased significantly (p〈0.05) after a simple-CHO diet (0.82±0.13 to 0.65±0.10 mmol l−1) but were unchanged after a complex-CHO diet. Blood glucose and lactate, and serum insulin were not altered following a CHO-rich diet.
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  • 29
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    Cell & tissue research 252 (1988), S. 9-15 
    ISSN: 1432-0878
    Keywords: Pancreas, endocrine ; Insulin ; Immunocytochemistry ; Lysosomes ; Crinophagy ; Mouse (NMRI)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ultrastructural studies of pancreatic islets have suggested that crinophagy provides a possible mechanism for intracellular degradation of insulin in the insulin-producing B-cells. In the present study, a quantitative estimation of crinophagy in mouse pancreatic islets was attempted by morphometric analysis of lysosomes containing immunoreactive insulin. Isolated islets were incubated in tissue culture for one week in 3.3, 5.5 or 28 mmol/l glucose. The lysosomes of the pancreatic B-cells were identified by morphological and enzyme-cytochemical criteria and divided into three subpopulations comprising primary lysosomes and insulin-positive or insulin-negative secondary lysosomes. Both the volume and numerical density of the primary lysosomes increased with increasing glucose concentration. The proportion of insulin-containing secondary lysosomes was highest at 5.5 and lowest at 3.3 mmol/l glucose. Insulin-negative secondary lysosomes predominated at 3.3 mmol/l glucose. Studies of the dose-response relationships of glucose-stimulated insulin biosynthesis and insulin secretion of the pancreatic islets showed that biosynthesis had an apparent Km-value for glucose of 7.0 mmol/l, whereas it was 14.5 mmol/l for secretion. The pronounced crinophagic activity at 5.5 mmol/l glucose may thus be explained by the difference in glucose sensitivity between insulin biosynthesis and secretion resulting in an intracellular accumulation of insulin-containing secretory granules. The predominance of insulin-negative secondary lysosomes at 3.3 mmol/l glucose may reflect an increased autophagy, whereas the predominance of primary lysosomes at 28 mmol/l glucose may reflect a generally low activity of intracellular degradative processes.
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  • 30
    ISSN: 1432-0878
    Keywords: Pancreas, endocrine ; Stomach ; Intestine ; Immunohistochemistry ; Thyrotropin-releasing hormone (TRH) ; Somatostatin ; Avian pancreatic polypeptide ; Insulin ; Gastrin ; Rat ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary By use of the indirect immunofluorescence technique, the cellular localization of thyrotropin-releasing hormone (TRH) was studied in the gastrointestinal tract of rats and guinea pigs of different ages. TRH-like immunoreactivity (LI) was observed in many pancreatic islet cells of young rats and guinea pigs but only in single cells of 6-month-old rats. In aged guinea pigs, a reduction in the number of TRH-positive cells was evident; however, numerous strongly fluorescent cells were still present. In the guinea pig, TRH-LI was in addition observed in gastrin cells in the stomach. TRH-positive nerve fibers occurred in the myenteric plexus of the oesophagus, stomach and intestine of the rat, and in the muscle layers of the guinea pig. These results suggest a functional role of TRH both as hormone and neuroactive compound in various portions and sites of the gastro-intestinal tract of the rat and guinea pig
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  • 31
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    Development genes and evolution 196 (1987), S. 527-530 
    ISSN: 1432-041X
    Keywords: Insulin ; Diapause termination ; Pieris brassicae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Due to its close structural homology with the 4K prothoracicotropic hormone isolated from Bombyx mori, we tested the ability of vertebrate insulin to break pupal diapause in a Lepidopteran, Pieris brassicae. Injection of 5μg of bovine insulin in diapausing pupae led to diapause termination and synchronous adult eclosion; the effect of insulin was dose-dependent. Bovine insulin-A chain and B chain injected separately failed to show any biological activity suggesting that the intact structure of the molecule is required. Bovine insulin also promoted adult development of decapitated diapausing animals. We show that insulin triggers a reactivation of the neuroendocrine system leading to a neosynthesis of ecdysone beginning 6 days after treatment. This neosynthesis also occurred in beheaded animals suggesting that insulin stimulates the prothoracic glands without acting via the brain.
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  • 32
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    Journal of molecular medicine 65 (1987), S. 169-173 
    ISSN: 1432-1440
    Keywords: Gastrin ; Insulin ; Omeprazole ; Somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of a 4-week treatment with the substituted benzimidazole omeprazole (20 mg daily) or placebo on gastric endocrine function was tested in healthy male volunteers. Compared with placebo-treated subjects basal serum gastrin levels were slightly but significantly increased after treatment with omeprazole from 10 to 22 pg/ml (medians;P〈0.05) but returned to pretreatment values after 2 weeks recovery (9 pg/ml). Antral gastrin tissue concentration increased and was still elevated after recovery; however, antral gastrin concentrations also increased in placebo controls, and increments immediately after cessation of omeprazole treatment (2.58 µg/g; median) were not significantly over control values (1.92 µg/g;P〉0.1). Postprandial gastrin release, basal and food-stimulated insulin release, antral somatostatin concentration, and volume densities of antral G and D cells were unaffected. It is concluded that, due to incomplete inhibition of gastric acid secretion at the omeprazole dose studied, only slight effects on the endocrine stomach are to be expected after 4 weeks of administration of omeprazole.
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  • 33
    ISSN: 1432-1106
    Keywords: Dorsomedial hypothalamic nucleus ; Ultradian growth hormone rhythm ; Insulin ; Body weight regulation ; Food intake ; Organismic set point
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Weanling male rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated animals served as controls. At the end of a 39-day postoperative period DMNL rats were lighter and shorter than controls and also exhibited significant hyopophagia. Their efficiency of food utilization (weight gained for the amount of food eaten) was normal, however. Subsequent determination of plasma growth hormone (GH) and insulin (IRI) levels every 15 min for 6-h periods from freely moving chronically cannulated rats showed no differences in pulsatile patterns and peaks of GH nor in plasma IRI levels between DMNL rats and controls. There was also no significant difference between mean 6-H GH and IRI concentrations between the two groups. The reduced body weight, length and food intake are apparently unrelated to the normal GH and IRI secretory patterns. In conjunction with previous data indicating normal somatomedin activity and normal responses to various homeostatic challenges, the data make a strong case for the argument that DMNL rats are not “growth-retarded”. Rather, they are normal animals that are “scaled-down” to a smaller size with maintenance of normal homeostatic capacity. This has been hypothesized to be due to the existence in these animals of an “organismic” set point.
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  • 34
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    European journal of pediatrics 146 (1987), S. 113-122 
    ISSN: 1432-1076
    Keywords: Prenatal growth ; Nutrition ; Insulin ; Placental lactogen ; Tissue growth factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The evidence reviewed here shows that the endocrinology of fetal growth is very different from that operating postnatally. Pituitary hormones play little part in stimulating growth of the lean body mass or skeleton although growth hormone (GH) may be involved, in some as yet ill defined way in the ontogeny of the fetal pancreatic islet and insulin secretion. Insulin is important because it stimulates fetal cellular anabolism but acts in a permissive manner: with too little insulin growth is inhibited, with too much growth proceeds at a genetically predetermined rate. Placental lactogen (PL), or other peptides within the GH/PL family, may act as a true growth-promoting hormone in the fetus; it stimulates both cellular metabolism and mitosis. The part played by endocrine control mechanisms in the fetus is set in context by an appreciation of the importance of locally acting tissue growth factors, and in particular the somatomedins. Their part in fetal growth control is intimately bound up with the plane of nutrition experienced by the fetus. It is concluded that the simplest analysis that makes biological sense involves a consideration of hormones, tissue growth factors and nutrition, not hierarchically but as mutually interacting variables.
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  • 35
    ISSN: 1432-1017
    Keywords: Insulin ; conformers ; molecular dynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Insulin crystallizes in different forms, some of which show different conformations for the different molecules in the asymmetric unit. This observation leads to the question as to which conformation the molecule will adopt in solution. Molecular dynamics computer simulations of rhombohedral 2 Zn pig insulin have been carried out for both monomers (1 and 2) independently in order to study their behaviour in the absence of quaternary structure and crystal packing forces. These preliminary 120 ps simulations suggest that both monomers converge in solution to very similar conformations which differ from the X-ray structures of both monomer 1 and 2 (Chinese nomenclature), but are closer to the former, as has previously been suggested by an analysis of the crystal packing (Chothia et al. 1983) and by energy minimization (Wodak et al. 1984). The secondary structure of the molecules is basically preserved, as expected. A detailed description of the conformational changes is given.
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  • 36
    ISSN: 1432-0428
    Keywords: Insulin ; mutant ; familial ; gene ; high performance liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We describe a family from Japan displaying the mutant insulin syndrome with hyperinsulinaemia and an increased insulin: C-peptide molar ratio. Serum insulin isolated from several family members showed reduced in vitro biological activity, and analysis by high performance liquid chromatography revealed a peak co-eluting with human insulin and a second species of increased hydrophobicity co-migrating with the previously reported Insulin Wakayama. The insulin genes from the propositus were cloned and sequenced, revealing one normal allele; the second allele, encoding a leucine for valine amino acid substitution at position 3 of the insulin A chain, was similar to that previously described for Insulin Wakayama. Synthesized [LeuA3] insulin showed 0.14% of receptor binding activity on rat adipocytes and a 10-fold prolonged half-life in a somatostatin-infused dog compared with human insulin. The finding of the same mutant gene in two unrelated Japanese families suggests that Insulin Wakayama may be discovered in additional Japanese families with hyperinsulinaemia and/or diabetes.
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  • 37
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    Diabetologia 30 (1987), S. 310-313 
    ISSN: 1432-0428
    Keywords: Insulin ; platelet aggregation ; euglycaemic clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To examine the effect of serum insulin independent of the level of blood glucose in vivo on platelet aggregation in healthy individuals, a euglycaemic insulin clamp was applied up to 4 h. During the clamp, blood glucose at 5.0 mmol/l and insulin levels at 100 μU/ml were maintained. Blood samples were drawn before, 2 and 4 h after the start of the insulin clamp. The platelet aggregation induced by 1 μmol/l and 2 μmol/l ADP, 1 μg/ml collagen and 2.7 μmol/l epinephrine was measured in the blood samples. Platelet aggregation induced by adenosine diphosphate, collagen and epinephrine in the 4 h sample was significantly reduced from the pre-clamp value of 8.4% to 3.9% (p〈0.05), 26.2% to 7.0% (p〈0.01) and 31.8% to 9.1% (p〈0.01), respectively. On the other hand, when the same individuals were infused with physiological saline and blood glucose (4.4 mmol/l) and insulin level (10 mIU/l) were kept within normal values, there was no difference between the values of induced platelet aggregation in samples drawn before and during the insulin infusion. It was concluded that hyperinsulinaemia reduces platelet aggregation in vivo when euglycaemia was maintained.
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  • 38
    ISSN: 1432-0428
    Keywords: Insulin ; proinsulin ; crinophagy ; insulin crystals ; degradation ; lysosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin is thought to be chemically stabilized within β-granules in the crystal form. The other major products of the β-granule, proinsulin and C-peptide, by contrast, are not thought able to crystallize. The physico-chemical properties of peptides in soluble or crystalline form are dramatically different. The ability of insulin to crystallize in the β-granule might thus explain why this peptide, but not proinsulin/Cpeptide, remains stable even after its introduction into lysosomes as occurs during granulolysis (crinophagy). We have now studied this by exposing proinsulin or insulin to lysosomal proteases in vitro. 125I-insulin in soluble form was found to be degraded at the same rate as 125I-proinsulin. Strikingly, however, when the labelled insulin was crystallized, its rate of degradation was decreased from 1.9 to 0.2 pmol/min. We take these data as confirmation that the insulin crystal is resistant to degradation, thereby possibly accounting for (a) the presence of insulin immunoreactivity within multigranular bodies, and (b) the unusually slow rate of degradation of insulin within B cells compared with that of other hormones in their cells of origin.
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  • 39
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    Diabetologia 30 (1987), S. 394-396 
    ISSN: 1432-0428
    Keywords: Insulin ; C-peptide ; radio-immunoassay ; haemolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Venous blood was taken at the end of a glucose infusion test in 19 individuals and divided into four aliquots, 3 of which were variably haemolysed by repeated passage through a 23-gauge needle to simulate traumatic venepuncture. Plasma insulin (measured by both a charcoal separation and a double-antibody method), C-peptide, and haemoglobin were measured in each aliquot, and haemolysis was also assessed visibly. A significant loss of immuno-assayable plasma insulin was found in samples with only a trace of visible haemolysis, with up to 90% lost in severely haemolysed samples. Plasma C-peptide was unaffected by haemolysis. This represents an additional advantage for the use of plasma C-peptide in assessing insulin secretion.
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  • 40
    ISSN: 1432-0428
    Keywords: Insulin ; blood pressure ; obesity ; healthy man ; oral glucose tolerance test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study, we have measured plasma insulin at fasting and following an oral glucose load and blood pressure after glucose load in 367 (247 non-obese, 120 obese) normotensive and untreated mildly hypertensive subjects. Overall, there was no independent association between fasting plasma insulin levels and blood pressure values. After controlling for age and body weight, a significant relationship between postglucose plasma insulin levels and diastolic blood pressure was found. When non-obese and obese subjects were examined separately, significant relationships were identified between postglucose plasma insulin levels and both systolic and diastolic blood pressure values in the former but not in the latter. A comparison of sex-, age-, and weight-matched hyperinsulinaemic vs normoinsulinaemic subjects showed that the former had significantly higher values of blood pressure only if not obese. These results demonstrate that the plasma insulin response to glucose is independently correlated with blood pressure.
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  • 41
    ISSN: 1432-0428
    Keywords: Insulin ; despentapeptide insulin ; deshexapeptide insulin ; negative cooperativity ; insulin demerisation ; lipogenesis ; insulin binding ; insulin metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The C-terminus of the insulin B chain is essential for dimerisation and expression of negative cooperativity. In order to evaluate the possible physiological role of these phenomena, we have studied the properties in vivo and in vitro of despentapeptide insulin (B 26–30 deleted), derived from beef insulin, and deshexapeptide insulin (B25–30 deleted), derived from pork insulin. These materials do not dimerise and have 15% and 0% retention of negative cooperativity respectively. Lipogenesis potencies in rat adipocytes were: despentapeptide insulin 19.9±0.3%; deshexapeptide insulin 19.9±1.5%. Binding potencies in adipocytes were: despentapeptide insulin 22.6±7.8%; deshexapeptide insulin 13.2±3.3%. Metabolic clearance rates were reduced compared to insulin (insulin = 19.1±0.9; despentapeptide insulin = 9.7±0.8; deshexapeptide insulin = 6.4±0.6ml·min−1·kg−1 at plasma concentration 0.5 nmol/l). Hypoglycaemic potencies were reduced for both analogues (40% and 30%) when calculated on the basis of plasma concentration although both analogues and insulin were equally effective at lowering plasma glucose concentration in equimolar doses. Plasma half-disappearance time was prolonged (despentapeptide insulin=7.3±0.5; deshexapeptide insulin=9.1±0.2 min). Both analogues were full agonists and conformed to the general relationship between in vitro and in vivo properties seen with a wide range of modified insulins. They resemble other analogues with modifications which reduce receptor affinity without impairing dimerisation or negative cooperativity. The results do not support a physiological role for dimerisation or negative cooperativity.
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  • 42
    ISSN: 1432-2013
    Keywords: Heart ; Myocyte ; Glucose ; Insulin ; Catecholimines ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of insulin, forskolin, isoproterenol, and epinephrine on 3-O-methylglucose (hexose) transport and cell cyclic AMP levels were determined in adult rat cardiomyocytes. Insulin stimulated hexose transport in these cells an average of 2.5-fold. Initial hexose transport rates at 1 mM hexose were 3.75×10−2 nmol/mg cell protein/second in the absence of insulin, and 8.25×10−2 nmol/mg cell protein/second in the presence of 12.3 μM insulin. Forskolin at 5 μM nearly abolished hexose transport within 3 s of exposure, but did not increase cell cyclic AMP concentrations within 9 s. The apparentK i for hexose transport inhibition was about 0.3 μM forskolin. Epinephrine and isoproterenol at 50 μM increased cell cyclic AMP 4-fold during 9 s exposure, but did not affect hexose transport. Treatment of cells with these catecholamines of forskolin for up to 99 s increased cell cyclic AMP, but only forskolin inhibited hexose transport. We coclude from these results that forskolin acts on hexose transport independent of its action on adenyl cyclase, and that cyclic AMP does not inhibit or stimulate hexose transport.
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  • 43
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    Psychopharmacology 93 (1987), S. 167-172 
    ISSN: 1432-2072
    Keywords: Opioid receptors ; Diabetes ; Hyperglycemia ; Insulin ; Naloxone ; Streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of opioid receptors in diabetes and hyperglycemia-induced analgesia was studied in male Sprague-Dawley rats. Animals maintained under controlled environmental conditions were used in all studies. Pain latency was determined by the hot plate test (55° C) and analgesy-meter force method. The results of these studies indicate that streptozotocin-induced diabetic animals have a significantly higher pain threshold (P〈0.01) than the control groups. The pain threshold was found to be diurnally controlled with a peak at the beginning of the light phase (1000 hours) and a trough at the end of the dark phase (0800 hours). Diabetes-induced analgesia was found to be reversed by both acute or chronic insulin administration. In another study, glucose-induced hyperglycemic rats were found to have a significantly higher pain threshold (P〈0.01) than control animals, with a peak occurring at the beginning of the dark phase (2000 hours), and a trough at the begining of the light phase (0800 hours). The administration of the opioid antagonist naloxone (2 mg/kg) reversed the hyperglycemia and diabetic-induced analgesia. The results of these studies might indicate that analgesia found in diabetic or hyperglycemic animals may be related to the endogenous opioid system.
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  • 44
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    Journal of anesthesia 1 (1987), S. 82-87 
    ISSN: 1438-8359
    Keywords: Blood glucose ; Glucose loading ; Insulin ; Epidural anesthesia ; Upper abdominal surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma glucose, insulin, glucagon, growth hormone (GH) and cyclic-AMP (C-AMP) were measured in 14 patients undergoing partial gastrectomy under 5 g/hr glucose loading. Seven patients received general anesthesia (GOF; Group G) and the other seven, GO + epidural anesthesia (analgesia Th4–L1; Group E). Blood glucose increased in both groups, although it remained consistently lower in Group E than in Group G. Serum IRI and IRI/glucose ratio appeared consistently higher in Group E than in Group G and a significant difference was found between the two groups at the early period of surgery. The changes in plasma glucagon and GH were found independent of those in glucose. Cyclic-AMP was also consistently higher in Group G than in Group E and a significant difference was observed at the end of anesthesia. These results suggest that epidural anesthesia with 5 g/hr glucose loading may facilitate insulin release from the islet and peripheral blood uptake particularly during the early period of surgery while many other factors such as GH, cortisol and vagal stimulation seemed to be involved in the later period of surgery. (Ogata M et al.: Clinical study of glucose metabolism during partial gastrectomy; comparison between epidural and general anesthesia. J Anesth 1: 82–87, 1987)
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  • 45
    ISSN: 1573-739X
    Keywords: Chromatography ; Drug stability ; Gamma rays ; Insulin ; Sterilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Partially purified insulin preparations of bovine and porcine origin, were subjected to gamma-irradiation with doses ranging from 1.0 up to 25 kGy (0.1–2.5 Mrad) at 0
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  • 46
    ISSN: 1439-6327
    Keywords: Supramaximal exercise ; Diet ; Blood glucose ; Insulin ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of supramaximal exercise on blood glucose, insulin, and catecholamine responses were examined in 7 healthy male physical education students (mean±SD: age=21±1.2 years; $$\dot V_{{\text{O}}_{{\text{2 max}}} } $$ =54±6 ml · kg−1 · min−1) in response to the following three dietary conditions: 1) a normal mixed diet (N); 2) a 24-h low carbohydrate (CHO) diet intended to reduce liver glycogen content (D1); and 3) a 24-h low CHO diet preceded by a leg muscle CHO overloading protocol intended to reduce hepatic glycogen content with increased muscle glycogen store (D2). Exercise was performed on a bicycle ergometer at an exercise intensity of 130% $$\dot V_{{\text{O}}_{{\text{2 max}}} } $$ for 90 s. Irrespective of the dietary manipulation, supramaximal exercise was associated with a similar significant (p〈0.01) increase in the exercise and recovery plasma glucose values. The increase in blood glucose levels was accompanied by a similar increase in insulin concentrations in all three groups despite lower resting insulin levels in conditions D1 and D2. Lactate concentrations were higher during the early phase of the recovery period in the D2 as compared to the N condition. At cessation of exercise, epinephrine and norepinephrine were greatly elevated in all three conditions. These results indicate that the increase in plasma glucose and insulin associated with very high intensity exercise, persists in spite of dietary manipulations intended to reduce liver glycogen content or increase muscle glycogen store. These data suggest that the blood glucose increase following supramaximal exercise is most likely related to hepatic glycogenolysis in spite of a substantial decrease in liver glycogen content.
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  • 47
    ISSN: 1432-0878
    Keywords: TRH ; Insulin ; Pancreas ; Streptozotocin ; Regeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Streptozotocin treatment at birth induces, in the pancreas of rats, first depletion of insulin and thyrotropin-releasing hormone and then early regeneration ofβ cells and insulin, but not TRH. This study was undertaken to investigate whether the reduction in pancreatic TRH content can be associated with changes in the intensity and the distribution of TRH-immunoreactivity, and to follow the pattern of regeneration ofβ cells through insulin- and TRH-immunoreactivity. In control animals, strong TRH-immunoreactivity was seen in insulin-containing cells on days 1–4 after birth. At day 7, the TRH-immunoreactivity was already decreased. In contrast, insulin-immunoreactivity was present throughout the neonatal period. A sparse population of cells near ducts also contained both TRH- and insulin-immunoreactivity at 1–2 days age. In streptozotocin-treated animals, TRH-immunoreactivity is found only in a few scattered insulin-containing cells in altered islets on days 1–4. Near the ducts, there were new insulin-containing cells which did not contain TRH. From day 7 regeneration of endocrine cells was characterized by new, typical islets, but these contained insulin-, but not TRH-immunoreactivity. These findings suggest a differential control of the biosynthesis of insulin and TRH within the pancreas.
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  • 48
    ISSN: 1432-0878
    Keywords: Anglerfish islet ; Oxytocin ; Insulin ; Innervation ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Recent reports indicate that oxytocin exerts direct effects on the release of insulin and glucagon from the endocrine pancreas of the rat. The purpose of this study was to determine whether oxytocin-like immunoreactivity is present in the anglerfish islet, and if it is associated with subsets of hormone-producing cells. Antisera against oxytocin, insulin, glucagon, somatostatin, neuropeptide Y, and the 200 — kd neurofilament polypeptide were applied to serial 5 μm sections of pancreatic islets. The antiserum to the 200 — kd neurofilament polypeptide labeled nerve bundles and axons, some of which were also stained with the oxytocin antiserum. Oxytocin immunoreactivity was observed in large nerves that branched into varicose fibers. These fibers were consistently associated only with clusters of insulin-producing cells. Successive application of oxytocin and insulin antisera to the same section provided additional verification of this relationship. Oxytocin-labeled nerves were not associated with cells immunoreactive to glucagon, somatostatin, or neuropeptide Y (anglerfish peptide Yg). The results demonstrate that oxytocin or an oxytocin-like peptide is located in fibers that surround only insulin-producing cells in the anglerfish islet. Although the functional significance of this observation remains to be determined, the results imply that oxytocin, or an oxytocin-like peptide, may affect the synthesis or release of insulin from anglerfish islets.
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  • 49
    ISSN: 1432-0878
    Keywords: Islets of Langerhans ; S-100 protein ; Insulin ; Glucagon ; Somatostatin ; Pancreatic polypeptide ; Neuro-insular complex ; Monkey, Macaca irus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary S-100 protein-immunoreactive cells were demonstrated by immunocytochemical procedures in the pancreatic islets of Langerhans in the monkey Macaca irus. By use of antibodies against human S-100 protein or bovine S-100 protein, these cells were observed in all islets in the head and tail portions of the pancreas. Immunostained cells were usually located in the center of the islets or sometimes found in a more widely distributed form, but they were never arranged in a regular concentric fashion. The number of immunoreactive cells varied from one islet to another but it was relatively limited making up only 0.75%–6.3% of all insular cells. With the use of the double-immunoenzymatic procedure for demonstration of the four main endocrine cell types (insulin-, glucagon-, somatostatin-and pancreatic polypeptide producing elements), it was possible to establish that S-100 protein-immunoreactive cells represent a distinct cell type. Antibodies against S-100 protein-stained neuroinsular complexes. The present findings speak in favor of a new cell type to be added to the large variety of S-100 protein-immunoreactive cells outside the central nervous system.
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  • 50
    ISSN: 1432-0878
    Keywords: Endocrine pancreas ; Insulin ; Glucagon ; Somatostatin ; Immunocytochemistry ; Neoceratodus forsteri (Australian lungfish)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The endocrine pancreas of the Australian lungfish,Neoceratodus forsteri, was investigated immunocytochemically for the presence of polypeptide hormone-producing cells. Three cell types were identified, namely insulin-, glucagon-, and somatostatin-immunoreactive elements. The insulin cells are confined solely to the center of the islets. Glucagon and somatostatin cells are distributed peripherally around the central mass of the insulin cells. Isolated cells or clusters of glucagon and somatostatin cells are also dispersed within the exocrine parenchyma. The immunoreactive cell types are compared with those staining with standard histological procedures. The spatial relationships of the different cell populations are examined.
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  • 51
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    Journal of molecular medicine 64 (1986), S. 1124-1130 
    ISSN: 1432-1440
    Keywords: Insulin ; Glucagon ; Glucose ; Hemodialysis ; Nifedipine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate long-term effects of nifedipine on carbohydrate and lipid metabolism, 15 hypertensive patients undergoing regular hemodialysis treatment were investigated before nifedipine therapy, after 3 and 9 weeks, and 2 weeks after stopping nifedipine therapy. Three weeks following the administration of nifedipine, both glucose and insulin concentrations decreased significantly from 102.1±2.6 to 94.9±2.2 mg/dl and from 19.9±2.9 to 13.9±1.7 µU/ml and also remained significantly lower after 9 weeks of nifedipine therapy. This effect was paralleled by a fall of noradrenaline and dopamine. Glucagon levels remained constant. Glucose tolerance tests performed during nifedipine medication and 2 weeks after stopping of nifedipine therapy did not differ significantly. An increase of pyruvate, citric acid cycle intermediates, and ketone bodies — but not of lactate — was registered during nifedipine medication. The observed effects were not completely abolished after the 2-week placebo phase. Our data indicate that nifedipine lowers serum glucose values despite decreased insulin and constant glucagon levels in hypertensive hemodialyzed patients. Considering additionally the behavior of catecholamines and organic acids, the effects could be explained by the improvement of peripheral glucose utilization.
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  • 52
    ISSN: 1432-1440
    Keywords: Type II diabetics ; Treatment of late failure with oral drugs ; Insulin ; Glibenclamide ; Combination treatment ; C-Peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a double-blind placebo-controlled cross-over study eight type II diabetics (three men, five women), of whom six were at the point of late failure to oral treatment, were given an insulin infusion of 22 U human insulin/patient for 45 min (∼7 mU/kg × min); 30 min before infusion either glibenclamide (1 tablet Euglucon N) or placebo was administered. Glucose in venous blood, C-peptide, insulin, and glibenclamide concentrations in the blood plasma were simultaneously determined over a period of 210 min. The monitoring of glucose was handled using a Biostator. The insulin level reached a mean maximum of 400 to 500 µU/ml and was in a behavior of 100 µU/ml for 60 min. The areas under the concentration-time curves (AUCs) were practically identical in the two regimes. The blood glucose fell (in mean) from 260 mg/dl to 135 mg/dl and at the end of the experiment was in the range of 155 mg/dl. The glibenclamide concentrations reached maximal concentrations of 185 ng/ml 90 min after administration. The C-peptide concentrations fell in the placebo phase by more than 40%. In contrast, in the glibenclamide period there was at first a slight rise and later a slight marginal fall (initial, 2.0 ng/ml vs 1.9 ng/ml; 60 min, 1.3 ng/ml vs 1.8 ng/ml; 180 min, 1.2 ng/ml vs 1.8 ng/ml). Values after 90, 120, and 180 min were statistically different. The AUCs (0–180 min) were different (329 ng × min/ml vs 251 ng × min/ml). The inhibition of insulin secretion (measured by C-peptide) caused by exogenous insulin administration is largely abolished by glibenclamide. This mechanism could be a major cause for the reduction of the insulin requirement in type II diabetics that has been shown in numerous clinical studies during simultaneous treatment with glibenclamide.
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  • 53
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    European journal of pediatrics 145 (1986), S. 73-76 
    ISSN: 1432-1076
    Keywords: Child ; Juvenile diabetes mellitus ; Insulin ; Drug dose response relationship ; Glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The magnitude of the disturbance of metabolic control in diabetes mellitus in very young children has been recognised, but seldom studied. Limitations to studies are set by the difficulty of obtaining control data and until recently the lack of alternative therapies. Recently “mini” pumps for continuous subcutaneous insulin delivery have become available and may offer an alternative therapeutic possibility. The present investigation has been undertaken to collect overnight metabolic data of very young diabetic children (〈6 years) controlled by standard injection therapy. During one admission to hospital frequent blood samples were collected for free insulin, glucose, alanine, lactate, glycerol and 3-hydroxybutyrate determinations. In all children (n=9) the profiles showed a steep rise in glucose from 04.30h (6.2±1.3 mmol/l) to 09.30h (17.8±2.4 mmol/l) (the so-called “dawn-phenomenon”). The nature of the changes in the intermediary metabolites suggested that rise in blood glucose was caused by insufficient insulin. We have attempted to explore the time relationship between the overnight drop in free insulin levels and the rises in blood glucose by a distribution-free statistical analysis, correlating successive changes in time between the two profiles. The analysis suggested a delay of 2–6 h between free insulin levels and their effects. In conclusion: a clear “dawn phenomenon” is seen in very young diabetic children, and contributes to their poor glycaemic control. More stable and higher insulin concentrations in the early morning, obtained perhaps by continuous subcutaneous insulin infusion, might ameliorate the overall glycaemic control in the very young diabetic child.
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  • 54
    ISSN: 1432-0428
    Keywords: Insulin ; noradrenaline ; isoprenaline ; bicyclic cascade system ; HMG CoA reductase ; ACAT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was concerned with the effect of insulin and catecholamines on the rate limiting enzymes of cholesterol metabolism in rat hepatocytes. Insulin was found to increase the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and to have no effect on the activity of acyl-coenzyme A: cholesterol-o-acyltransferase. Noradrenaline and isoprenaline increased the activities of both 3-hydroxy3-methyl glutaryl coenzyme A reductase and acyl-coenzyme A: cholesterol-o-acyltransferase. The effect of noradrenaline or isoprenaline in the presence of insulin was that of a lower stimulatory response on 3-hydroxy-3-methyl glutaryl coenzyme A reductase but comparable to that found with either catecholamine alone. The combination of either catecholamine with insulin had no effect on the activity of acyl-coenzyme A: cholesterol-o-acyltransferase. These observations suggest that the activities of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and acyl-coenzyme A: cholesterol-o-acyltransferase are regulated independently by insulin in the presence or absence of catecholamines. By contrast, catecholamines appear to regulate both enzyme activities in a similar fashion.
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  • 55
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    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 71-76 
    ISSN: 1432-1912
    Keywords: Insulin ; 2-Deoxy-d-glucose ; Capsaicin ; Glucoreceptors ; Adrenaline ; Blood glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effect of insulin and of 2-deoxy-d-glucose (2-DG) on adrenaline secretion was compared in rats pretreated as neonates with capsaicin and in rats pretreated with the drug-vehicle. 2. Capsaicin-pretreatment did not inhibit the fall in blood glucose concentrations induced by insulin or by fasting, nor did it affect the increase in blood glucose concentrations in response to 2-DG or restraint stress. 3. Capsaicin greatly reduced the rise in urinary adrenaline excretion over 24 h and the fall in the adrenaline content of the adrenal glands normally induced by insulin. 4. In contrast, capsaicin-pretreatment did not interfere with the rise in the adrenaline excretion and the fall in the adrenaline content of the adrenal glands normally induced by 2-DG. 5. Insulin-induced hypoglycaemia as well as intracellular glucopenia in the brain caused by 2-DG activate hypothalamic centres which stimulate the nervous input to the adrenal medulla and adrenaline secretion. The fact that capsaicin interfered only with the adrenal effect of insulin suggests the involvement of afferent C-fibres in this insulin effect. 6. Injection into the hepatic portal vein of a C-fibre stimulating dose of capsaicin increased arterial glucose concentrations in vehicle-pretreated rats but not in capsaicin-pretreated rats. The response was significantly diminished after bilateral vagotomy. 7. From the present results it is concluded that glucose receptors in the hepatic portal vein transmit signals via afferent, capsaicin sensitive C-fibres to the brain and that activation of this pathway is essential for the increase in adrenaline secretion elicited by insulin-induced hypoglycaemia.
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  • 56
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    Research in experimental medicine 186 (1986), S. 203-208 
    ISSN: 1433-8580
    Keywords: Acute hepatic failure ; Insulin ; Glucagon ; Glucagon-like peptides ; Blood-brain barrier ; Thalamus-hypothalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin contents in the thalamus-hypothalamus were significantly increased in acute hepatic failure dogs treated with dimethylnitrosamine. Glucagon immunoreactivity (GI) contents also tended to increase in the same portion of the brain. However, insulin and GI contents in the cerebral cortex and midbrain did not rise. Glucagon-like immunoreactivity (GLI) contents were much higher than GI in all the brain regions tested, but the levels were not significantly altered in hepatic failure dogs. A simultaneous infusion of insulin and glucagon to hepatic failure dogs failed to produce an elevation of insulin, GI and GLI contents even in the thalamus-hypothalamus.
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  • 57
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    Cellular and molecular life sciences 42 (1986), S. 58-60 
    ISSN: 1420-9071
    Keywords: Insulin ; islets ; ethanol ; adrenergic receptors ; cyclic AMP ; theophylline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This study was done to delineate the role of α- and β-adrenergic receptors and cyclic AMP in the mechanism of ethanol effects on insulin release from isolated islets. Rats were given an α-adrenergic blocker, phentolamine, or a β-adrenergic blocker, propranolol. In addition, ethanol 1 g/kg was given intragastrically 1 h prior to sacrifice. Glucose mediated insulin release from isolated islets was enhanced by phentolamine and decreased by propranolol. Ethanol treatment inhibited glucose-induced insulin release from isolated islets of control rats as well as those given phentolamine and/or propranolol. Insulin release from isolated islets in response to dibutyryl-cyclic AMP was attenuated by ethanol. Theophylline enhanced glucose mediated insulin release from control islets but ethanol treatment produced a significant inhibition of insulin response. The data suggest that the site of action of the deleterious effects of ethanol on insulin release from isolated islets in rat does not involve adrenergic system and cyclic AMP.
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  • 58
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    Annals of biomedical engineering 14 (1986), S. 257-276 
    ISSN: 1573-9686
    Keywords: Insulin ; Controlled release micropump ; Basal delivery ; Diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract A model has been developed to describe the delivery of insulin from a controlled release micropump (CRM). Basal delivery was provided by diffusion due to a concentration difference driving force across the CRM. This was modelled by considering the CRM to be a series of one-dimensional steady-state diffusion resistances. This delivery model was used to size prototypes and identify the piston, foam and the pump outlet as the controlling resistances to basal insulin transport. Augmented delivery by the CRM was achieved by repeated compression of a foam disk by a mild steel piston which was driven by a solenoid (tested voltage range 0–173 V DC; 5 msec “on” time; frequency 20–40 min−1). The increased delivery was attributed to the combination of mixing inside the pump barrel and displacement of barrel contents into the downstream reservoir. This action was approximated by a three-compartment model, which considered the CRM to consist of a well-mixed upstream reservoir and pump barrel (with a downstream reservoir) separated by two resistances: a constant upstream membrane resistance, (KmAm)−1, and a variable downstream mixing rate resistance, (Qd)−1. A least squares fit of the model to experimental data showed Qd to increase with the cube of the force on the piston and linearly with the compression frequency. In agreement with experimental results, the model predicted the upstream membrane to be rate controlling only at augmented pump resistances close to the value (KmAm)−1. These models were used to design an improved prototype (VIII) which is now being evaluated in vivo in pancreatectomized dogs for its efficacy in restoring and sustaining normoglycemia.
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  • 59
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    European journal of applied physiology 55 (1986), S. 236-239 
    ISSN: 1439-6327
    Keywords: Aerobic exercise ; Equal oxygen uptake ; Growth hormone ; Lactate ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five normal men, aged 23 to 35 years, participated in two bouts of continuous aerobic cycling separated by five days. The first type of exercise (EI) was cycling at a pedalling frequency of 50 rev · min−1 with a load which produced a steady state O2 uptake of approximately 40% of the subjects' $$\dot V_{O_{_2 max} } $$ . The second type of exercise (EII) was cycling at a pedalling frequency of 90 rev · min−1 with a load such that an equal steady state $$\dot V_{O_2 } $$ was reached and maintained. Both EI and EII lasted 40 min. GH levels increased in EI and EII, reaching their maximum at 8 min of recovery (245 and 300% of resting values, respectively). No significant differences were observed between EI and EII in GH, lactate, glucagon, insulin, cortisol and glucose levels between the two exercises. While it has been reported earlier that GH levels were frequently related to lactate levels and/or decreased O2 availability (Sutton 1977; Raynaud et al. 1981; Kozlowski et al. 1983; VanHelder et al. 1984a, b), this study suggests that the opposite is also valid, that is, different types of exercise of equal $$\dot V_{O_2 } $$ , duration and lactate production do not produce significantly different GH responses.
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  • 60
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    European journal of applied physiology 55 (1986), S. 445-449 
    ISSN: 1439-6327
    Keywords: Exercise ; Intermediary metabolism ; Insulin ; Non-esterified fatty acids ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic and hormonal response during squash was observed in eight normal men. Significant increases from resting were found for blood glucose, lactate, pyruvate, alanine and glycerol while total ketone bodies and plasma nonesterified fatty acids rose after play stopped. Insulin and C-peptide decreased significantly and catecholamines, ACTH, prolactin and growth hormone increased.
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  • 61
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    European journal of applied physiology 55 (1986), S. 315-317 
    ISSN: 1439-6327
    Keywords: Glucagon ; Hyperthermia ; Catecholamines ; Insulin ; Glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma glucagon, adrenaline, noradrenaline, insulin and glucose concentrations were measured in 7 healthy young males during hyperthermia in a sauna bath: plasma glucagon levels increased from baseline values of 127.0±12.9 (SEM) pg · ml−1 to a maximum of 173.6±16.1 (SEM) pg · ml−1 at the 20th min of exposure. No change in plasma insulin and a slight increase in plasma glucose concentration were seen. Since a concomitant moderate increase in plasma catecholamine levels was also present, the adrenergic stimulus is believed to trigger glucagon release during hyperthermia. Diminished visceral blood flow, known to occur in sauna baths, may cause a decrease in the degradation of plasma glucagon and thus contribute to the elevated plasma glucagon levels.
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  • 62
    ISSN: 1432-0878
    Keywords: Peripheral neurosecretory structures ; Immunocytochemistry ; Insulin ; Glucagon ; AKH ; Insects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Insulin, glucagon and adipokinetic hormone antisera were applied to the corpora cardiaca, perisympathetic organs, neurohemal areas and peripheral neurosecretory cells of three insect species, the locust Locusta migratoria, the cockroach Periplaneta americana, and the stick insect Carausius morosus. The neurohemal part of the corpora cardiaca was shown to be immunoreactive to both insulin and glucagon antisera while the glandular cells reacted to adipokinetic hormone antisera. The perisympathetic organs seem to be devoid of these three substances, but certain peripheral neurohemal areas contained AKH and glucagon immunoreactive products. The latter were found to originate in the peripheral neurosecretory cells.
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  • 63
    ISSN: 1432-0878
    Keywords: Neonatal hepatocytes ; Peptide mitogens ; Epidermal growth factor/Urogastrone ; Glucagon ; Insulin ; Cell proliferation ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In untreated primary cultures of neonatal rat liver kept in high-calcium (1.8 mmol/l), foetal bovine serum (10%v/v)-containing minimal essential medium (FBSMEM), the absolute numbers of hepatocytes did not change between day 4 and day 9 because ongoing cell loss was counterbalanced by proliferation of a discrete sub-population of the cells. By contrast, the number of stromal cells increased linearly with time. Growth of hepatocytes and stromal cells was differently affected by the daily addition, between day 4 and day 8 of culture, of fresh medium to which peptide mitogen(s) in concentrations ranging from 10-14 to 10-8 mol/l had been added. Epidermal growth factor/urogastrone (EGF/URO) with or without equimolar mixtures of glucagon and insulin, induced first hyperplasia of hepatocytes and stromal cells and then apopotosis (degeneration and death) of the progeny of the stimulated cells. By contrast, equimolar mixtures of glucagon and insulin caused a progressive increase in the number of hepatocytes and stromal cells unbalanced by any increase in cell death. At subphysiological concentrations glucagon, in synergism with EGF/URO and/or some other unknown heat-stable component of serum, acted as a trophic factor for hepatocytes. By contrast, insulin alone did not enhance growth of hepatocytes, but rather blocked the mitogenic effects of EGF/URO. The three hormones exerted neither mitogenic nor apoptotic effects when administered in a low calcium (0.01 mmol/l) FBS-MEM medium. These results reveal that EGF/URO may control the size of cell populations in neonatal liver by calcium-dependent mechanisms that make it unlikely to be a promoter of hepatocyte tumours. They also show that glucagon acts as a positive trophic regulator for hepatocytes.
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  • 64
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    New York, NY [u.a.] : Wiley-Blackwell
    Cell Biochemistry and Function 4 (1986), S. 19-24 
    ISSN: 0263-6484
    Keywords: Insulin ; peptide hormone receptor ; prostatic epithelial cells ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Insulin receptors have been characterized in rat prostatic epithelial cells by using [125I]insulin and a variety of physicochemical conditions. The binding data at equilibrium (2h at 15°C) could be interpreted in terms of two populations of insulin receptors: a class of receptors with high affinity (Kd = 2·16 nM) and low binding capacity (28·0 fmol mg-1 protein), and another class of receptors with low affinity (Kd = 0·29 μM) and high binding capacity (1·43 pmol mg-1 protein). Proinsulin exhibited a 63-fold lower affinity than insulin for binding sites whereas unrelated peptides were ineffective. The specific binding of insulin increased by about 50 per cent after 96 h of fasting; this increase could be explained by an increase of both the number of the high affinity-low capacity sites and the affinity of the low affinity-high capacity sites. These results together with previous studies on insulin action at the prostatic level strongly suggest that insulin may exert a physiological role on the prostatic epithelium.
    Additional Material: 4 Ill.
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  • 65
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    Diabetologia 28 (1985), S. 458-463 
    ISSN: 1432-0428
    Keywords: Insulin ; insulin stability ; insulin delivery systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Exposure of insulin solutions to elevated temperatures for prolonged periods of time will inevitably lead to chemical modifications of the hormon. Contact with different materials in dosing devices, other design-related factors and motion appear to be chemically more detrimental than storage in glass vials at the same temperature. An in vitro test, designed to mimick the in vivo situation, consisted of delivery of insulin at 37 °C while the device was constantly moved on a shaking apparatus. Insulin quality was assessed using high performance liquid chromatography. A polyethylenepoly-propylene glycol-stabilized neutral human insulin solution (HOE 21 PH) was used. A single insulin derivative is the major modification product which, after passage of the complete infusion system, amounts to up to 10%. The biological potency of the derivative is indistinguishable from native insulin. Delivery of acidic insulin under implant conditions, leads to extensive and multiple insulin derivatization, even though the biological potency remains 95% after 4 weeks.
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  • 66
    ISSN: 1432-0428
    Keywords: Insulin ; myocardial contraction ; heart rate ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the acute effects of intravenous insulin on myocardial contractility and heart rate, echocardiography was performed in 12 healthy subjects and continuous heart rate recording in 11 healthy subjects before and during eugly-caemic insulin and glucose infusion. The rate of insulin infusion was 0.5–1.0 mU·kg−1·min−1. Serum insulin concentration was increased from 14.1±5.5 (mean±SD) to a plateau level of 91.3±22.8 mU/l. Left ventricular end-diastolic diameter, ejection phase indices and the heart rate remained at basal levels during the intervention. Thus moderate hyperinsulinaemia, induced by euglycaemic insulin and glucose infusion, has no inotropic or chronotropic effects in healthy supine subjects.
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  • 67
    ISSN: 1432-0428
    Keywords: Insulin ; free insulin assay ; insulin antibodies ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma insulin concentrations of insulin-treated diabetic patients must be measured after removal of insulin antibodies, usually by precipitation with polyethylene glycol (PEG). Details of the procedure vary between laboratories; commonly, frozen plasma is thawed and incubated at 37 °C to restore a presumed equilibrium between free and antibody bound insulin before extraction. The present study was designed to investigate methodological factors that could affect the measured free insulin concentration. In normal subjects PEG extraction of globulins did not disturb measurement of insulin concentrations, whether carried out after incubation for 2 h at 37 °C, or storage at -20 °C, in either order. Freezing or incubation of PEG extracts of plasma from insulin-treated patients also failed to disturb the measured concentrations of free insulin. When plasma from patients was incubated for 2 h after storage, a marked scatter (51–272%) of measured results occurred when compared to bedside extraction. This problem was not overcome by buffering with HEPES or storage at a lower temperature (-40 °C). Incubation at 0 °C also severely disturbed the apparent concentrations. Incubation of plasma before extraction and freezing also disturbed the measured result, a problem not corrected by maintaining near physiological pH. Total insulin concentrations measured on acid extracts were not disturbed by any of these manoeuvres. The temperature of centrifugation of blood at the time of venepuncture did not influence the result. Furthermore, when insulin concentrations were rising or falling similar percentage changes were seen over a 30-min incubation of plasma before extraction on the day of venepuncture, suggesting that equilibrium between free and bound insulin is maintained in vivo. We suggest that, for accurate estimation of free insulin concentrations in insulin-treated diabetic patients, immediate centrifugation of blood and extraction of insulin antibodies is mandatory.
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  • 68
    ISSN: 1432-0428
    Keywords: Insulin ; proinsulin ; insulin-like growth factors ; multiplication-stimulating activity ; insulin effects on growth ; embryogenesis ; chick embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The teratogenic effect of insulin in early vertebrate embryos is controversial and the mechanisms involved are unknown. We studied the effects of pharmacological doses of insulin in chick embryos during the period of differentiation. We compared the effects of insulin with two proinsulins, desoctapeptide-insulin and multiplication-stimulating activity, peptides that have little insulin-like metabolic activity while they have significant growth effects. Chick embryos at 46 h of development were injected with the different peptides. At 96 h the mortality and abnormal growth elicited by the peptides were dose-dependent. Considering the indices of lethality (LD50) and affected embryos (ED50) as 100% for insulin, proinsulin was 59–66% as potent as insulin, desoctapeptide-insulin 2–6% and multiplication-stimulating activity 176–204%. In the surviving embryos, insulin (5 μg, decreased DNA, RNA and protein content by 49%, 40% and 48% respectively compared with controls. The effects of insulin were not corrected by simultaneous glucose injections. These data suggest that insulin, at pharmacological doses, interferes with embryo development through a non-metabolic pathway, probably via a growth-type receptor.
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  • 69
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    Diabetologia 28 (1985), S. 295-301 
    ISSN: 1432-0428
    Keywords: Insulin ; insulin resistance ; obesity ; exercise ; glucose metabolism ; glycogen synthase ; fructose 2–6 bisphosphate ; skeletal muscle ; goldthioglucose obese mice ; hypertrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of work-induced hypertrophy (without any concomitant change in circulating parameters) on skeletal muscle metabolism was studied in lean mice and in goldthioglucose obese-mice. Soleus muscle was functionally overloaded in one leg by tenotomy of gastrocnemius muscle 4 days before muscle isolation, muscle in the other leg being used as control. Basal deoxyglucose uptake and glycolysis were markedly increased in overloaded muscles compared with control muscles, together with a ten-fold increase in fructose 2–6 bisphosphate content. In the presence of maximally effective insulin concentrations, deoxyglucose uptake and glycolysis were identical in overloaded and control muscles of lean mice, while the effects of overload and insulin were partly additive in muscles of goldthioglucose-obese mice. The sensitivity to insulin and insulin binding to muscles were not modified in overloaded muscles. Insulin-stimulated glycogenogenesis was decreased by about 50% probably due to a lower amount of glycogen synthase in overloaded than in control muscles. Thus, in muscles of goldthioglucose-obese mice work-induced hypertrophy increased the response to maximal insulin concentrations without modifying the altered insulin sensitivity and decreased insulin binding.
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  • 70
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    Experimental brain research 61 (1985), S. 87-90 
    ISSN: 1432-1106
    Keywords: Prostaglandins ; Brain ; Insulin ; 2-deoxy glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prostaglandin synthesis in the brain has been suggested as a component in the control mechanism of the cerebral circulation. During insulininduced hypoglycemia there is a significant increase in local cerebral blood flow in various brain regions, however, regional loss of autoregulation occurs under these conditions. In the present study the regional distribution of PGE2, TXB2 (the stable metabolite of thromboxane) and 6-keto-PGF1α (the stable metabolite of prostacyclin) was determined in rat brain following decapitation. Three groups of rats were treated with either saline, insulin or 2-deoxyglucose and their brains were rapidly removed one hour later. Samples from the cortex hypothalamus, hippocampus, striatum, nucleus accumbens and cerebellum were assayed by RIA for the content of PGE2, TXB2 and 6-keto-PGF1α The levels of all three compounds in control rats were the lowest in the striatum and cerebellum, while in the cortex and hippocampus their levels were 4–6 times higher. Insulin had selective effect on the post decapitation levels of prostanoids. It increased PGE2 in the n. accumbens and TXB2 in the hippocampus, and reduced 6-keto-PGF1α and TXB2 in the cortex. 2-DG reduced all PGs in the cortex and 6-keto-PGF1α in the hypothalamus and hippocampus. The results demonstrate that discrete brain areas have a differential capacity to accumulate PGs following decapitation. This capacity is selectively affected by insulin and 2-DG.
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  • 71
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    European journal of pediatrics 143 (1985), S. 183-186 
    ISSN: 1432-1076
    Keywords: C-peptide ; Growth hormone deficiency ; Obesity ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The daily excretion of C-peptide in the urine was measured in 105 healthy infants and children from birth to 14 years of age. For technical reasons no studies were performed from 1–3 years of age. The excretion of C-peptide showed a close positive correlation with age and weight. The relationship with weight was already apparent in the 1st days of life. The C-peptide/weight and the C-peptide/creatinine ratios were constant throughout most of childhood with the exception of the age range of 1 month-1 year when the C-peptide/creatinine was significantly higher. In obese children the C-peptide/weight and C-peptide/creatinine ratios were similar to those found in children with normal weight. In growth hormone deficiency these ratios were low and increased during the 1st week of growth hormone therapy. It is concluded that urinary C-peptide is a reliable indicator of integrated insulin production and gives new information about insulin secretion in various conditions.
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  • 72
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    Pflügers Archiv 405 (1985), S. S33 
    ISSN: 1432-2013
    Keywords: Sodium transport ; Epithelial transport ; Transport regulation ; Frog skin ; Oxytocin ; Ouabain ; Insulin ; Neurohypophysial hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1. Application of transepithelial square voltage pulses to the frog skin leads to responses in the transepithelial current and intracellular potential which include transient components. Determinations at 600 ms allow for meaningful estimates of basolateral membrane responses to transport modifiers. 2. Oxytocin produced a large and sustained increase in the amiloride-inhibitable short circuit current (I m) which was accompanied by a large increase of both apical and basolateral membrane conductance (g a andg b, respectively). WhileI m andg a increased nearly simultaneously,g b started to increase several minutes after the increase in the two other parameters. 3. Insulin also increasedI m,g a andg b. As with oxytocin, the increases inI m andg a often preceded the changes ing b. 4. Ouabain reducedI m andg a. The effects ofg b were more complex, since sometimes the inhibition ofI m was first accompanied by an increase followed by a decrease while in other instances only minor changes in conductance could be observed. 5. The currently available information regarding the control of cytoplasmic [Ca2+] and the effects of Ca2+ on cell membrane properties are used to construct a model in which changes in cytoplasmic [Ca2+] account for the observed behavior of the basolateral membrane.
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  • 73
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    Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 253-257 
    ISSN: 1432-1912
    Keywords: Clonidine ; Insulin ; Glucose ; Hyper-responsiveness ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effect of chronic clonidine treatment on the response to glucose of rat pancreatic B-cells was investigated. Clonidine treatment was carried out for 10 days by dissolving the drug into drinking water at a concentration of 10 μg/ml. Control rats were given drug-free tap water. Serum insulin responses to glucose (750 mg/kg, i. v.) of clonidinetreated rats were much smaller than those of control rats. However, after 1 day's withdrawal of clonidine, the rise in the serum insulin level induced by glucose was approximately 2-fold larger in clonidine-treated rats as compared to that in control rats. Since clonidine treatment decreased body weight of the rat by 10%–20% in 10 days, the same experiments were carried out with rats whose body weight loss was made comparable to that of clonidine-treated rats by restricting food for 10 days. Then, some animals of the group thus treated had food-restriction discontinued for 1 day. In both of the above two groups, no increment in glucoseinduced rise in serum insulin level was observed. Islets of Langerhans isolated from clonidine-treated rats showed pronounced insulin releasing capacity in response to glucose. Insulin content per islet of the clonidine-treated rat was slightly larger than that of control rat. These results indicate that the enhancement of serum insulin response to glucose following clonidine treatment is mainly attributable to the hyper-responsiveness developed in the pancreatic B-cells.
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  • 74
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    Clinical rheumatology 4 (1985), S. 294-300 
    ISSN: 1434-9949
    Keywords: Insulin ; Hyperostosis ; DISH ; New Bone Formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tendency of patients with DISH towards obesity or an adult onset of diabetes has been reflected in marked hyperinsulinaemia following glucose challenge. It is hypothesized that insulin at prolonged and high physiologic levels promotes new bone growth, particularly in the entheseal regions. These areas are also subject to various mechanical forces. The resulting new bone produces the radiological changes which characterise DISH.
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  • 75
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    European journal of applied physiology 54 (1985), S. 337-342 
    ISSN: 1439-6327
    Keywords: Exercise ; Anaerobic ; Aerobic ; Cortisol ; Glucagon ; Insulin ; Lactate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five normal men, aged 20–30 years, participated in three types of exercise (I, II, III) of equal duration (20 min) and total external work output (120–180 kJ) separated by ten days of rest. Exercises consisted of seven sets of squats with barbells on the shoulders (I; Maximal Power Output $$\dot W$$ max=600−900 W), continuous cycling at 50 rev · min−1 (II; $$\dot W$$ max=100−150 W) and seven bouts of intermittent cycling at 70 rev · min−1 (III; $$\dot W$$ max=300−450 W). Plasma cortisol, glucagon and lactate increased significantly (P〈0.05) during the exercise and recovery periods of the anaerobic, intermittent exercise (I and III) but not in the continuous, aerobic exercise (II). No consistent significant changes were found in plasma glucose. Plasma insulin levels decreased only during exercise II. The highest increase in cortisol and glucagon was not associated with the highest $$\dot V_E $$ , $$\dot V_{O_2 } $$ , $$\dot W$$ max or HR; however it was associated with the anaerobic component of exercise (lactic acid). It is suggested that in exercises of equal duration and total external work output, the continuous, aerobic exercise (II) led to lowest levels of glucogenic hormones.
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  • 76
    ISSN: 1439-6327
    Keywords: Glucose storage ; Insulin ; Exercise-training ; Athletes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was designed to evaluate the contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity characterizing endurance athletes. Plasma glucose and insulin were measured during an oral glucose tolerance test (OGTT) in six endurance athletes. Glucose storage and lipid oxidation during this test were also determined using indirect calorimetry. These measurements were compared to those obtained in five non-trained subjects who were tested before and during the three days following a 90-min cycle ergometer exercise performed at 69% of their $$\dot V_{{\text{O}}_{{\text{2max}}} }$$ . As expected, preexercise values of non-trained subjects revealed a much higher insulin response to glucose, and a lower glucose storage and lipid oxidation compared to results obtained in endurance trained individuals. Glucose tolerance was comparable in both groups. The morning following the exercise test, i. e. about 16 h after exercise, glucose storage was significantly increased in non-trained subjects to a level similar to that found in trained subjects. Surprisingly, this was accompanied by higher values of glucose during the OGTT without significant changes in insulinaemia. This impairment in glucose homeostasis was transitory since glucose tolerance had returned to control level on day 2 after exercise. At that time, the increase in glucose storage was less pronounced than in day 1. On day 3 after exercise, glucose and insulin responses to glucose were similar to preexercise values. These results indicate that the increase in glucose storage by acute exercise is not systematically associated with an improved glucose homeostasis, suggesting that other adaptive mechanisms also contribute to the improvement of insulin sensitivity in endurance athletes.
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  • 77
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    European journal of applied physiology 54 (1985), S. 420-426 
    ISSN: 1439-6327
    Keywords: Glycemia ; Glucose infusion ; Diet ; Free fatty acids ; Insulin ; Exercise in humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extant literature dealing with metabolic and hormonal adaptations to exercise following carbohydrate (CHO) reduced diets is not sufficiently precise to allow researchers to partial out the effects of reduced blood glucose levels from other general effects produced by low CHO diets. In order to shed light on this issue, a study was conducted to examine the effects of a 24-h CHO-poor diet on substrate and endocrine responses during prolonged (75 min; 60% $$\dot V_{O_{2max} } $$ ) glucose-infused leg exercise. Eight subjects exercised on a cycle ergometer in the two following conditions: 1) after a normal diet (CHON), and 2) after a 24-h low CHO diet (CHOL). In both conditions, glucose was constantly infused intravenously (2.2 mg · kg−1 · min−1) from the 10th to the 75th min of exercise in relatively small amounts (10.4±0.8 g). No significant differences in blood glucose concentrations were found between the two conditions at rest and during exercise although a significant increase (p〈0.01) in glucose level was observed in both conditions after 40 min of exercise. The CHOL as compared to the CHON condition, was associated with significantly (p〈0.05) lower resting concentrations of insulin, muscle glycogen (8.7 vs 10.6 g · kg−1), and triacylglycerol, and greater concentrations of Β-hydroxybutyrate (0.5 vs 0.2 mmol · L−1), and free fatty acids. During exercise, the CHOL condition as compared to the CHON condition, was associated with significantly (p〈0.05) lower insulin and R values, as well as greater free fatty acid (from min 20 to 60) and epinephrine (min 60 to 75) concentrations. Norepinephrine and glucagon concentrations also showed a net tendency (p〈0.06) to be higher in the CHOL condition. There were no significant differences at rest and during exercise in blood lactate and cortisol concentrations between the two conditions. These results demonstrate that blood glucose is not the sole determinant of the metabolic and hormonal responses during prolonged exercise following a low CHO intake and indicate that other factors may be involved in the regulatory mechanism.
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  • 78
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    Cell & tissue research 239 (1985), S. 537-545 
    ISSN: 1432-0878
    Keywords: Mouse ; Pancreas, endocrine ; Insulin ; Acid phosphatase ; Lysosomes ; Crinophagy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The relation between qualitative and quantitative glucose-dependent alterations of lysosomes in pancreatic islets and the function of the islets was studied. Isolated islets of the mouse were maintained in tissue culture for one week in either 28, 5.5 or 3.3 mmol/l glucose. Insulin biosynthesis, insulin secretion and insulin content of the cultured islets were determined. After culture, the islets were subjected to acid phosphatase cytochemistry and examined by electron microscopy and ultrastructural morphometry. Islets cultured in 28 mmol/l glucose both produced and secreted insulin rapidly. Such islets seemed, however, unable to maintain more than small amounts of granule-stored insulin. Islets cultured at the lower concentrations of glucose displayed a reduced insulin secretion, which apparently resulted in considerable amounts of intracellularly stored insulin. In all cultured islets different types of lysosomes, identified by their acid phosphatase reactivity, could be seen. Dense bodies, i.e., lysosomes characterized by a homogeneous, very fine, particulate content of high density, seemed to predominate at all concentrations of glucose. It is suggested that, in the islets, the dense bodies correspond morphologically to primary lysosomes. Other types of lysosomes with inclusions of various kinds, which were frequent at the two lower concentrations of glucose, may correspond to secondary lysosomes. Morphometry revealed differences between the size distributions of lysosomes in the three experimental groups. Thus, the average lysosomal size was inversely proportional to the concentration of glucose in the culture medium. However, the numerical density of lysosomes was greatest at the highest glucose concentration. The observation of secondary lysosomes, containing material resembling secretory granules, suggests that the increased size and lowered number of lysosomes in islets cultured at low glucose concentrations may depend on a crinophagic process. Such a process, together with insulin biosynthesis and insulin secretion, may be of physiological importance for control of the secretory granule content within the pancreatic B-cell.
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    Diabetologia 5 (1969), S. 325-330 
    ISSN: 1432-0428
    Keywords: Insulin ; proinsulin ; blood sugar ; mice ; rats ; pancreatectomy ; nephrectomy ; hepatectomy (partial) alloxan diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez les rats et les souris le taux du sucre sanguin est abaissé par une proinsuline obtenue à partir de l'insuline bovine (Schmidt et Arens [6]). Chez les rats alimentés et les souris à jeun, le rapport d'activité proinsuline: insuline est de 1∶4, chez les rats à jeun de 1∶2, dans le cas de dose équimolaire et en mesurant l'abaissement maximum du sucre sanguin. L'abaissement du sucre sanguin évolue de façon plus lente après proinsuline qu'après insuline. La proinsuline, incubée in vitro avec la trypsine, agit quantitativement et au point de vue temps, comme l'insuline. Chez les rats pancréatectomisés, chez les rats néphrectomisés ainsi que chez ceux hépatectomisés aux deux tiers, l'action de la proinsuline est la même que chez les animaux normaux. Les souris rendues diabétiques par l'alloxane répondent également à la proinsuline comme les souris intactes. L'action hypoglycémiante de la proinsuline se manifeste de façon retardée probablement parce que l'insuline active doit tout d'abord se former par un processus protéolytique dépendant du facteur temps. Ceci pourrait être aussi la raison pour laquelle, Rubenstein et coll. [5] signalent l'absence d'effet de la proinsuline dans le test de convulsion chez la souris.
    Abstract: Zusammenfassung An Ratten und Mäusen wird der Blutzucker durch ein aus Rinderinsulin gewonnenes Proinsulin (Schmidt und Arens [6]) gesenkt. Bei gefütterten Ratten und nüchternen Mäusen ist das WirkungsVerhältnis Proinsulin: Insulin = 1∶4, bei nüchternen Ratten 1∶2, wenn äquiznolar dosiert und das Maximum der Blutzuckersenkung gewertet wird. Die Blutzuckersenkung verläuft nach Proinsulin protrahierter als nach Insulin. Proinsulin, welches in vitro mit Trypsin inkubiert wurde, wirkt quantitativ und zeitlich wie Insulin. Bei pankreatektomierten, bei nephrektomierten und bei zweidrittelhepatektomierten Ratten wirkt Proinsulin ebenso wie an Normaltieren. Auch alloxandidbetische Mäuse sprechen auf Proinsulin wie intakte Mäuse an. Die hypoglykämische Wirkung des Proinsulins tritt wahrscheinlich deshalb verzögert ein, weil das aktive Insulin in einem zeitabhängigen proteolytischen Prozeß erst entstehen muß. Dies könnte auch die Ursache für eine von Rubenstein et al. [5] zitierte, fehlende Wirkung von Proinsulin im Mäusekrampftest sein.
    Notes: Summary Proinsulin obtained from bovine insulin (Schmidt and Arens [6]) lowered the blood sugar level of rats and mice. The activity ratio proinsulin: insulin was 1∶4 in fed rats and fasted mice, and 1∶2 in fasted rats, based on an equimolar dosage and measuring the effect in terms of maximum lowering of the blood sugar value. After proinsulin the decrease of the blood sugar was more protracted than after insulin. Proinsulin which was incubated with trypsin in vitro, resembled insulin in degree and onset of action. In pancreatectomized, nephrectomized and two-thirds hepatectomized rats proinsulin acted as in normal animals. Alloxan-diabetic mice responded to proinsulin like intact mice. The reason why the onset of the hypoglycaemic action of proinsulin was delayed is probably due to the fact that the active insulin must first be produced by a time-dependent proteolytic process. This may also be the cause of the ineffectiveness of proinsulin in the mouse convulsion test which was quoted by Rubenstein et al. [5].
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    Diabetologia 5 (1969), S. 143-145 
    ISSN: 1432-0428
    Keywords: Insulin ; galactose ; galactokinase ; deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez deux adultes souffrant d'une déficience en galactokinase la charge orale de galactose a été suivie d'une hypergalactosémie prolongée sans aucune élevation de l'insuline immunoréactive plasmatique.
    Abstract: Zusammenfassung Orale Belastung mit Galactose führte bei zwei Erwachsenen mit Galactokinasemangel zu einer prolongierten Hypergalactosämie, aber nicht zu einem Anstieg des immunoreaktiven Insulins im Plasma.
    Notes: Summary Oral galactose loading in two galactokinase-deficient adults produced the expected high and prolonged rise of galactose in peripheral blood, but no rise of circulating immunoreactive insulin.
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  • 81
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    Diabetologia 5 (1969), S. 195-197 
    ISSN: 1432-0428
    Keywords: Insulin ; glucagon ; adipose tissue ; lipolysis ; FFA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé A des concentrations proches de celles qui sont rencontrées dans le plasma humain, le glucagon stimule fortement la lipolyse au niveau de la graisse épididymaire du rat, étudiéein vitro. Les effets de telles concentrations de glucagon sont réduits, voire abolis par l'insuline aux concentrations de 25 et 100μU/ml. Rapprochées de l'effet insulinogénique puissant du glucagon, ces observations peuvent fournir une explication quant au caractère retardé de l'élévation du taux sanguin des acides gras libres observée après injection de glucagonin vivo.
    Abstract: Zusammenfassung Glucagon stimuliert in Konzentrationen, wie sie auch im menschlichen Plasma vorkommen, die Lipolyse im Ratten-Nebenhodenfettgewebein vitro stark. Die Effekte derartiger Glucagonkonzentrationen werden durch Insulin (25–100μE/ml) verringert bis aufgehoben. Unter Berücksichtigung der ausgeprägten Wirkung von Glucagon auf die Insulinfreisetzung können diese Beobachtungen eine Erklärung für die Verzögerung des Anstiegs der freien Fettsäuren im Serum liefern, die man nach Glucagoninjektionenin vivo beobachtet.
    Notes: Summary Glucagon in concentrations similar to those found in human plasma markedly stimulates lipolysis in rat adipose tissuein vitro. The effects of these “physiological” concentrations of glucagon are reduced or abolished by insulin at concentrations of 25 and 100μU/ml. Considering the marked insulinogenic effect of glucagon these observations may provide an explanation for the delayed increase of blood FFA observed after glucagon injectionin vivo.
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    Diabetologia 5 (1969), S. 61-66 
    ISSN: 1432-0428
    Keywords: Insulin ; islets of Langerhans ; mouse ; collagenase ; glucose ; mannoheptulose ; glucagon ; adrenaline ; phentolamine ; theophylline ; tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La libération de l'insuline pendant l'incubation des îlots de Langerhans de la souris, isolés après digestion du pancréas par la collagénase, a été étudiée, et l'influence de divers facteurs sur la vitesse de libération a été recherchée. Le glucose à 3.0 mg/ml (glucose élevé) stimulait la libération d'insuline, mais n'avait pas d'effet à 0.6 mg/ml (taux bas). Le mannoheptulose bloquait la stimulation provoquée par du glucose élevé, comme le faisait l'adrénaline. L'effet de l'adrénaline était aboli par la phentolamine, un agent bloquant alpha adrénergique. Le glucagon seul, ainsi qu'en pre'sence d'un taux de glucose bas, stimulait la libération d'insuline, mais non de façon constante avec un taux de glucose élevé. L'adrénaline abolissait la stimulation provoquée par le glucagon. La théophylline stimulait la libération lorsque le glucose était bas, mais beaucoup moins lorsque le glucose était élevé et pas du tout avec le glucagon, quelle que soit la concentration de glucose. Le tolbutamide stimulait la libération d'insuline avec une faible concentration de glucose et cet effet n'était pas inhibé par l'adrénaline. La convenance de cette préparation pour des études sur le métabolisme des cellules insulaires et sa relation avec la sécrét ion d'insuline est discutée.
    Abstract: Zusammenfassung Es wurde die Insulinausschüttung aus Langerhans'schen Inseln von Mäusen, die durch Kollagenase-Behandlung des Pankreas gewonnen worden waren, untersucht und der Einfluß verschiedener Faktoren auf die Freisetzungsgeschwindigkeit überprüft. Eine hohe Glucose-Konzentration von 3.0 mg/ml förderte die Insulin-Ausschüttung, während die niedrige Konzentration von 0.6 mg/ml keine Wirkung ergab. Mannoheptulose und Adrenalin blockierten die Stimulation durch die hohe Glucosekonzentration. Der AdrenalinEffekt konnte durch Phentolamin, eine alpha-Rezeptoren blockierende Substanz, wieder aufgehoben werden. Glucagon führte allein und in Gegenwart der niedrigen Glucosekonzentration zu einer verstärkten Insulininkretion: dies war jedoch bei Kombination mit der hohen Glucosekonzentration nicht konstant der Fall. Adrenalin hob die Stimulierung durch Glucagon auf. Theophyllin führte bei Gegenwart der niedrigen Glucosekonzentration zu einer gesteigerten Ausschüttung, dieser Effekt trat unter der höheren Glucosekonzentration in wesentlich geringerem Umfang und bei Zusatz von Glucagon und einer der beiden verwandten Glucosekonzentrationen überhaupt nicht auf. Bei niedriger Glucosekonzentration stimulierte Tolbutamid die Insulinfreisetzung; dieser Effekt ließ sich durch Adrenalin nicht aufheben. Die Aussagefähigkeit dieses Präparates für Untersuchungen des Inselzell-Stoffwechsels und seiner Beziehungen zur Insulininkretion wird diskutiert.
    Notes: Summary The release of insulin during incubation of mouse islets of Langerhans, isolated after digestion of the pancreas with collagenase, has been studied, and the influence of various factors on the rate of release investigated. Glucose at 3.0 mg/ml (high glucose) stimulated insulin release, but had no effect at 0.6 mg/ml (low glucose). Mannoheptulose blocked the stimulation by high glucose, as did adrenaline. The adrenaline effect was abolished by phentolamine, an alpha-adrenergic blocking agent. Glucagon alone, stimulated insulin release, and also with low glucose, but not consistently with high glucose. Adrenaline abolished the stimulation by glucagon. Theophylline stimulated release with low glucose, much less so with high glucose and not at all with glucagon at either glucose concentration. Tolbutamide stimulated release with low glucose, and this effect was not inhibited by adrenaline. The suitability of this preparation for studies of islet cell metabolism and its relationship to secretion of insulin is discussed.
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  • 83
    ISSN: 1432-0428
    Keywords: Insulin ; mouse tissues ; kidney fluorescence microscopy ; microscopy ; autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La localisation d'insuline marquée avec I125 ou avec de l'isothiocyanate de fluorescéine a été étudiée au moyen d'autohistoradiographie au microscope optique, au microscope électronique et au moyen de microscopie à fluorescence dans les tissus de souris à jeun et de souris alimentées normalement. L'hormone fluorescente a été trouvée dans les cellules des tubules proximaux du rein de souris à jeun seulement, tandis que l'hormone radioactive a été repérée aussi dans le rein de souris alimentées, bien qu'en quantité inférieure à celle trouvée chez les souris à jeun. Au microscope électronique la radioactivité est présente dans le rein dans la bordure en brosse, les vacuoles et les mitochondries apicales et le noyau, mais pas dans l'appareil de Golgi ou dans les lysosomes. —L'hormone radioactive est aussi présente dans les autres tissus mais sans différence quantitative entre les souris à jeun et les souris alimentées. Les auteurs concluent que le procédé de ré-absorption de l'insuline par les cellules des tubules proximaux du rein est spécifique: l'hormone n'est pas dégradée de la même façon que les autres protéines mais probablement stockée afin de contrôler les processus métaboliques relevant des organelles subcellulaires dans lesquelles elle se trouve.
    Abstract: Zusammenfassung Gefütterte und fastende Mäuse erhielten fluoreszierendes oder mit125J markiertes Insulin i.v. Die Lokalisation des Insulins in den Geweben wurde untersucht. Nur bei Tieren im Hungerzustand fand sich das fluoreszierende Hormon in den Nieren, während sich das radioaktive Insulin bei gefütterten und fastenden Tieren in den proximalen Tubulusschlingen der Nieren nachweisen ließ. Die fastenden Tiere schienen dabei mehr Radioaktivität aufzuweisen. Wurden die Nieren unter Verwendung von Techniken mit hohem Auflösungsvermögen untersucht, so fand sich die Radioaktivität im Bürstensaum, in den apikalen Vakuolen und Mitochondrien und dem Kern, jedoch nicht im Golgi-Apparat oder den Lysosomen. Alle anderen Gewebe enthielten Hormon-Radioaktivität, aber weder ihre Menge noch ihre Lokalisation unterschieden sich bei gefütterten und fastenden Tieren. Es wird gefolgert, daß der Prozeß der Insulinabsorption durch die Zellen der proximalen Tubulusschlingen spezifisch ist und daß das Hormon nicht in ähnlicher Weise wie andere Eiweißkörper abgebaut wird. Wahrscheinlich kommt es über eine Speicherung zu einer Steuerung der entsprechenden Stoffwechselprozesse in den subzellulären Organellen, in denen das Hormon sich befindet.
    Notes: Summary Starved and fed mice were injected intravenously with either fluorescent or125I-insulin and the localization of the hormone was investigated in various tissues. The fluorescent hormone was found in the kidney of starved animals only, whereas the radioactive hormone was found in the proximal convoluted tubule cells of the kidney of both fed and fasted animals, although the latter group appeared to contain more radioactivity than the first. With high resolution techniques the radioactivity in the kidney was found in the brush border, the apical vacuoles, the apical mitochondria and the nucleus, and never in the Golgi apparatus or the lysosomes. All other tissues contained radioactivity due to the hormone, but no difference in either the amount or the localization was found between fed an starved animals. It is concluded that the process of absorption of insulin by the cells of the proximal convoluted tubules is specific and that the hormone is not degraded in a way similar to other proteins, but is likely to be stored and to control cellular metabolic processes from its sites of localization.
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  • 84
    ISSN: 1432-0428
    Keywords: Insulin ; 32P incorporation ; adenine nucleotides ; guanine nucleotides ; Na+K+ ATP-ase ; ouabain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le but de ces investigations a été de contribuer à la compréhension du mécanisme d'action de l'insuline, en provoquant un turn-over accru du phosphate inorganique marqué au32P, en ATP et autres mononucléotides, dans le diaphragme du rat. Pendant l'incubation du diaphragme intact de rat dans un milieu bicarbonaté de Krebs Ringer, sans addition de substrat, on n'a pas observé d'effet de l'insuline sur le contenu en adénine-nucléotides, en guanine-nucléotides, y compris le 3′5′ AMP cyclique et le 3′5′ GMP cyclique. Quand du phosphate inorganique radioactif marqué au32P était présent dans le milieu, l'insuline augmentait l'activité spécifique du phosphate inorganique intracellulaire et provoquait une incorporation accrue du32P dans l'ATP et le GTP. L'effet sur l'ADP était moins prononcé. Il a été montré que ces effets de l'insuline dépendent de la composition ionique du milieu et du transport membranaire des ions. L'augmentation due à l'insuline de l'activité spécifique du phosphate inorganique intracellulaire et du marquage accru au32P de l'ATP (et du GTP) était en grande partie inhibée par l'ouabaïne. Pendant l'incubation dans les milieux où le chlorure de sodium a été remplacé isoosmotiquement par le chlorure de potassium ou de choline, les effets de l'insuline décrits ci-dessus étaient abolis. Les résultats indiquent que le marquage accru de l'ATP (et du GTP) provoqué par l'insuline, peut être en premier lieu attribué à des phénomènes survenant au niveau de la membrane cellulaire. L'augmentation de l'activité spécifique du phosphate inorganique intracellulaire en présence d'insuline, peut s'expliquer par une captation accrue du phosphate inorganique marqué au32P, à partir du milieu. Apparemment le marquage accru au32P de l'ATP (et du GTP) est une conséquence secondaire. On suggère que cet effet de l'insuline est d'abord en rapport avec un effet sur les enzymes de la membrane, en particulier sur l'ATP-ase activée par Na+, K+ et Mg2+.
    Abstract: Zusammenfassung Ziel dieser Untersuchungen war es, zu einem besseren Verständnis der stimulierenden Wirkung von Insulin auf den Einbau von anorganischem32P Phosphat in ATP und andere Mononucleotide im Rattenzwerchfell beizutragen. Während der Inkubation intakter Rattenzwerchfelle in Krebs-Ringer-Bicarbonat Puffer ohne Substratzusatz konnte kein Insulineffekt auf den Gehalt an Adenonucleotiden und Guaninnucleotiden, sowie von cyclischem 3′,5′ AMP und cyclischem 3′,5′ GMP beobachtet werden. In Gegenwart von anorganischem32P Phosphat steigerte Insulin die spezifische Aktivität von intrazellulärem anorganischen Phosphat und bewirkte einen verstärkten Einbau von32P in ATP und GTP. Die Wirkung auf ADP war weniger ausgeprägt. Es konnte gezeigt werden, daß diese Insulineffekte von dem IonenGehalt des Mediums und dem Membrantransport der Ionen abhängen. Die Steigerung der spezifischen Aktivität des anorganischen Phosphates und der Markierung von ATP (und GTP) mit32P ließ sich weitgehend durch Ouabain wieder aufheben. Bei Inkubation in Pufferlösungen, die statt NaCl isoosmolare Mengen von KCl oder Cholinchlorid enthielten, waren die oben erwähnten Insulineffekte nicht mehr nachweisbar. Die Resultate sprechen dafür, daß die verstärkte Markierung von ATP (und GTP) unter Insulin in erster Linie auf Vorgängen an der Zellmembran beruht. Die erhöhte spezifische Aktivität des intrazellulären anorganischen Phosphates in Gegenwart von Insulin läßt sich durch einen verstärkten Einstrom von32P Phosphat aus dem Medium erklären. Augenscheinlich kommt es dadurch sekundär zu einer gesteigerten32P Markierung von ATP (und GTP). Wir möchten annehmen, daß dieser Insulineffekt vorwiegend über die Membranenzyme erfolgt und sich vor allem auf die Na+, K+ und Mg++ aktivierbare ATPase erstreckt.
    Notes: Summary The aim of these investigations has been to contribute to an understanding of the mechanism of action of insulin in promoting increased turn over of32P inorganic phosphate into ATP and other mononucleotides in the rat diaphragm. During incubation of the intact rat diaphragm in Krebs Ringer bicarbonate medium without addition of substrate, no effect of insulin on the content of adenine nucleotides and guanine nucleotides including cyclic 3′,5′ AMP and cyclic 3′,5′ GMP has been observed. When32P radioactive inorganic phosphate was present in the medium, insulin increased the specific activity of intracellular inorganic phosphate and promoted an increased incorporation of32P into ATP and GTP. The effect on ADP was less pronounced. It has been shown that these effects of insulin depend upon the ionic composition of the medium and on ion membrane-transport. The insulin-promoted increase of specific activity of intracellular inorganic phosphate and of increased32P labelling of ATP (and GTP) was to a great extent inhibited by ouabain. During incubation in media where sodium chloride had been iso-osmotically replaced by potassium chloride or choline chloride, the above mentioned effects by insulin were abolished. The results indicate that the increased labelling of ATP (and GTP) promoted by insulin can be primarily attributed to events occuring at the cell membrane. The increased specific activity of intracellular inorganic phosphate in the presence of insulin can be explained by increased uptake of32P inorganic phosphate from the medium. Apparently the increased32P labelling of ATP (and GTP) occur as a secondary consequence. It is suggested that this insulin effect is primarily concerned with an effect on membrane enzymes, particularly the Na+, K+, Mg2+ activated ATP-ase.
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  • 85
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    Diabetologia 5 (1969), S. 304-308 
    ISSN: 1432-0428
    Keywords: Insulin ; bile ; rabbit ; 125I-insulin ; glucose ; galactose ; fructose ; tolbutamide ; phenformin ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On trouve de l'insuline immunoréactive dans la bile hépatique de lapins normaux. Moins de 1% d'une dose injectée d'insuline bovine atteint la bile. Quand de l'insuline bovine 125I, seule ou liée à l'anticorps, est administrée par voie intraveineuse, seulement 40% de la radioactivité retrouvée dans la bile est précipitable avec l'acide trichloracétique et moins de 10% réagit avec le sérum anti-insuline de cobaye. Le glucose, le fructose le galactose, le tolbutamide et la phenformine provoquent tous une élévation de l'insuline dans la bile, qui atteint son maximum 40 à 50 min après l'injection. L'alloxane atténue ou abolie ces réponses.
    Abstract: Zusammenfassung Immunoreaktives Insulin wird in der Leber-Galle normaler Kaninchen gefunden. Weniger als 1% einer injizierten Dosis von Rinder-Insulin erreicht die Galle. Wenn man reines oder an Antikörper gebundenes 125I-Rinderinsulin intravenös verabreicht, lassen sich mit Hilfe von Trichloressigsäure nur 40% der Radioaktivität ausfällen, die in der Galle gefunden wird, und weniger als 10% reagieren mit Meerschweinchen-Anti-Insulinserum. Glucose, Fructose, Galaktose, Tolbutamide und Phenformin verursachen ein Ansteigen von Insulin in der Galle, welches ein Maximum innerhalb von 40 bis 50 Min. nach der Injektion erreicht. Alloxan vermindert oder hebt diese Effekte auf.
    Notes: Summary Immuno-reactive insulin is found in the hepatic bile of normal rabbits. Less than 1% of an injected dose of bovine insulin reached the bile. When 125I-bovine insulin alone or complexed with antibody was given intravenously, only 40% of the radioactivity recovered in the bile was precipitable with trichloracetic acid, and less than 10% reacted with guinea pig anti-insulin serum. Glucose, fructose, galactose, tolbutamide and phenformin all caused an elevation in bile insulin, which reached a maximum 40 to 50 min after the injection. Alloxan attenuated or abolished these responses.
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  • 86
    ISSN: 1432-1912
    Keywords: Amiloride ; Insulin ; Glucose Transport ; Leucine Incorporation ; Isolated Adipose Tissue ; Amilorid ; Insulin ; Glucosetransport ; Leucineinbau ; isoliertes Fettgewebe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Die Aufnahme von Glucose ins isolierte epididymale Fettgewebe und die Bildung von 14CO2 aus [1-14C]-Glucose wurde als Maß von Transportvorgängen, die Incorporation von [1-14C]-Leucin ins Fettgewebsprotein als Maß der Proteinsynthese vor und nach Zusatz von Amilorid in vitro verwendet. 2. Amilorid setzt den Transport durch die Membran sowohl ohne als auch mit Stimulierung durch Insulin halbmaximal in 10−4 M-Konzentration herab. Aus der Kinetik des Transportes kann geschlossen werden, daß Amilorid die maximale Geschwindigkeit des gesamten Vorganges verlangsamt, ohne die Transportkonstante zu verändern. 3. Der Einbau von Leucin ins Fettgewebsprotein wird durch Amilorid in 3 · 10−4 M-Konzentration auf ein Zehntel herabgesetzt. Das Verhalten von [1-14C]-α-Aminoisobuttersäure läßt den Schluß zu, daß der Aminosäuretransport durch die Membran des Fettgewebes nicht beeinflußt wird. 4. Die Wirkungen des Amilorids am Fettgewebe entsprechen im Prinzip denjenigen des Triamterens und des 6-Aminonicotinsäureamids. Ebenso ist allen gemeinsam, daß sie den renalen Natrium- und Kaliumtransport im distalen Abschnitt des Nephrons hemmen. 5. Es ist möglich, daß ein Zusammenhang zwischen den hemmenden Wirkungen dieser Pharmaka auf den Leucin-Einbau in das Fettgewebsprotein und der Störung von Transportvorgängen durch biologische Membranen besteht.
    Notes: Summary 1. The uptake of glucose and the formation of 14CO2 from [1-14C]-glucose were used as a measure of transport processes, and the incorporation of [1-14C]-leucine into the protein of adipose tissue served as a measure of protein synthesis before and after the addition of amiloride to the isolated epididymal adipose tissue of the rat in vitro. 2. In a concentration of 10−4 M, amiloride decreases the glucose transport through tissue membranes by 50% with and without stimulation by insulin. It can be deduced from the kinetics of the transport that amiloride slows down the maximal velocity of the complete process without influencing the transport constant. 3. The incorporation of leucine into adipose tissue protein was diminished to 10% by amiloride in a concentration of 3 × 10−4 M. Experiments with [1-14C]-α-aminoisobutyric acid allow the conclusion that the amino acid transport through the membrane of the adipose tissue remains uninfluenced. 4. The effects of amiloride on the adipose tissue are similar to those of triamterene and of 6-aminonicotinamide. In addition, they all inhibit renal sodium and potassium transport in the distal part of the nephron. 5. It is possible, that there is a connection between the inhibiting effects of these drugs on the incorporation of leucine into the protein of adipose tissue and the disturbance of transport processes through biological membranes.
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  • 87
    ISSN: 1432-2013
    Keywords: Toad Bladder ; Sodium Transport Pool ; Aldosterone ; Insulin ; Vasopressin ; Krötenblase ; Natrium-Transport-Pool ; Aldosteron ; Insulin ; Vasopressin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The size of toad bladder sodium transport pool, defined as that amount of sodium of apical origin and recovered in tissue at equilibrium, was compared with sodium transport rate, derived from short-circuit current read immediately before tissue analysis. Provided certain precautions be taken, the relationship between both variables can be described by a curve starting at the intersect ofX (pool, in μEq) andY (transport, in μEq/hr) axes, with a tendency forX to increase faster thanY. Assuming sodium transport pool forms one compartment, its calculated half-life averages 2–3 min. sodium transport pool measurements are thought to shed light on mechanism of sodium transport by toad bladder because pool size was large with respect to transport rate when tissue was exposed to several inhibitors of sodium transport. Conversely, upon stimulation of activity of (substrate — depleted) preparations by glucose, a relative reduction of pool size was observed. Aldosterone, vasopressin (and adenosine 3′,5′-phosphate) increased sodium pool size and transport rate, proportionately; insulin stimulated sodium transport more than it increased pool size. Thus, insulin presumably exerts its effect at the sodium “pump” while such a site of action need not be postulated for aldosterone and vasopressin: these 2 hormones would instead induce, permeability changes faciliting sodium movement at the apical border of toad bladder epithelial cells.
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  • 88
    ISSN: 1432-5233
    Keywords: Glybenclamide ; Insulin ; Insulin secretion ; Sulfonylureas ; Tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Les effets métaboliques de la glybenclamide et de la tolbutamide ont été étudiés chez deux groupes de sujets normaux traités avec des doses comparables des deux sulphanylurées. En rapport aussi à la dose de 1:400, la glybenclamide a démontré une activité insuline-sécrétive bien majeure de celle de la tolbutamide. La réponse insulinique a été suivie par une rapide et prolongée diminution des NEFA sériques et par un moins persistant effet hypoglycémique. Les effets métaboliques de l'HB 419 sont encore évidents 10–12 heures après l'administration du médicament, tandis que l'activité de la tolbutamide est terminée géneralement entre 4–6 heures. Quand l'administration des médicaments a été pratiquée en concomitance avec une charge veineuse de glucose, le coéfficient de Conard était élevé d'une façon significative par toutes les deux sulphanylurées.
    Abstract: Resumen Los efectos metabólicos de la glibenclamida y de la tolbutamida han sido investigados en dos grupos de sujetos normales tratados con dosis comparables de las dos sulfanilúreas. Inclusive en una relación de dosificación de 1:400, la glibenclamida ha demostrado una actividad insulinosecretora mucho mayor de la tolbutamida. La respuesta insulínica ha sido seguida de una disminución pronta y prolongada de los NEFA séricos y de un efecto hipoglucemiante menos persistente. Los efectos metabólicos del HB 419 son aún evidentes a las 10–12 horas después de la administración del medicamento, mientras la actividad de la tolbutamida es anulada por lo general dentro de 4–6 horas. Cuando la suministración de los medicamentos ha sido practicada en coincidencia con una carga venosa de glucosa, el coeficiente de Conard apareció significativamente elevado por ambas sulfanilúreas.
    Notes: Riassunto Gli effetti metabolici della glibenclamide e della tolbutamide sono stati indagati in 2 gruppi di soggetti normali trattati con dosi comparabili delle due sulfaniluree. Anche in un rapporto di dosaggio di 1:400, la glibenclamide ha mostrato un'attività insulino-secretiva assai maggiore di quella della tolbutamide. La risposta insulinica è stata seguita da una pronta e prolungata diminuzione dei NEFA serici e da un meno persistente effetto ipoglicemico. Gli effetti metabolici del-l'HB 419 sono ancora evidenti 10–12 h dopo la somministrazione del farmaco mentre l'attività della tolbutamide si annulla generalmente entro 4–6 h. Quando la somministrazione dei farmaci è stata praticata in coincidenza con un carico venoso di glucosio, il coefficiente di Conard è apparso significativamente innalzato da entrambe le sulfaniluree.
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  • 89
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    Acta diabetologica 6 (1969), S. 371-388 
    ISSN: 1432-5233
    Keywords: Insulin ; Insulin antibodies ; Insulin assay ; Laboratory technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 90
    ISSN: 1432-5233
    Keywords: Insulin ; Insulin antibodies ; Islets of Langerhans ; Placenta ; Transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Ce travail est la continuation des communications préliminaires sur la résistance insulinique des nouveaux-nés de mères insuline-résistantes. Les recherches ont été conduites sur cobayes et sur sujets humains. Les AA. ont démontré que les anticorps anti-insuline passent dans la circulation fœtale et provoquent l'apparition d'une insuline-résistance passive qui va disparaître dans les premières semaines de la vie. Les anticorps contre l'insuline bovine lient en partie l'insuline endogène des cobayes, ce qui est mis en evidence par l'hyperglycémie élevée des cobayes jeunes nées de mères insuline-résistantes. Les anticorps anti-insuline n'ont aucun effet important sur la structure du pancréas des cobayes dans la période périnatale.
    Abstract: Resumen Este trabajo representa la continuación de las comunicaciones preliminares sobre la resistencia insulínica que presentan las personas nacidas de madres insulino-resistentes. Las investigaciones han sido efectuadas en cobayas y hombres. Se ha demostrado que los anticuerpos anti-insulina pasan al círculo fetal, provocando la aparición de insulino-resistencia pasiva, que desaparece durante las primeras semanas de vida. Los anticuerpos contra la insulina bovina ligan en parte la insulina endógena de cobayas, como lo demuestra la hiperglucemia elevada de las cobayas jóvenes nacidas de madres insulino-resistentes. Los anticuerpos anti-insulina no ejercen ningún efecto apreciable sobre la estructura del páncreas de las cobayas durante el período peri-natal.
    Notes: Riassunto Questo lavoro rappresenta la continuazione delle comunicazioni preliminari sulla resistenza insulinica dei nati di madri insulino-resistenti. Le ricerche sono state condotte su cavie e su uomini. E' stato dimostrato che gli anticorpi anti-insulina passano nel circolo fetale inducendovi la comparsa di una insulino-resistenza passiva che scompare nelle prime settimane di vita. Gli anticorpi contro l'insulina bovina legano in parte l'insulina endogena di cavie, come è evidenziato dall'elevata iperglicemia delle cavie giovani nate da madri insulino-resistenti. Gli anticorpi anti-insulina non esercitano alcun effetto di rilievo sulla struttura del pancreas delle cavie nel periodo perinatale.
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  • 91
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    Acta diabetologica 6 (1969), S. 197-205 
    ISSN: 1432-5233
    Keywords: Diurnal variations ; Food intake ; Glucose load ; Insulin ; Tolbutamide test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume On a étudié l'effet de la lumière et de la période d'ingestion des aliments sur l'élimination d'insuline par les urines. On peut démontrer l'existence d'un rythme circadien et la présence de deux facteurs de régulation pour cette élimination. On présente quelques hypothèses concernant ces phénomènes.
    Abstract: Resumen Se estudió el efecto que sobre la eliminación de insulina urinaria ejercen los períodos de luzoscuridad y el horario de administración del alimento. Se demuestra la existencia de un ritmo circadiano de eliminación de dicha hormona, describiéndose dos reguladores del mismo. Se hacen especulaciones fisiopatológicas acerca de su significado.
    Notes: Riassunto E' stato studiato l'effetto della luce e del periodo di ingestione del cibo sull'eliminazione di insulina nelle urine. Si può dimostrare l'esistenza di un ritmo circadiano e la presenza di due fattori di regolazione per questa eliminazione. Vengono presentate alcune ipotesi concernenti questi fenomeni.
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  • 92
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    Acta diabetologica 6 (1969), S. 796-808 
    ISSN: 1432-5233
    Keywords: Desensitization ; Immunoglobulins ; Insensitivity ; Insulin ; Insulin allergy ; Insulin antibodies ; Macroglobulins ; Porcine insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Cinq patients atteints d'allergie à l'insuline ont été désensibilisés par de l'insuline de porc selon la méthode d'Urbach et Gotlieb. Le diagnostic d'allergie à l'insuline a été posé sur la base des manifestations cliniques, de la positivité des réactions cutanées et, dans 2 cas, des réactions de Prausnitz-Küstner (P.K.). On a obtenu dans 3 cas une désensibilisation. La présence d'anticorps anti-insuline a été révélée par la méthode immunoautoradiographique en employant de l'insuline131J. Avant la désensibilisation la présence d'anticorps IgG a été enregistrée chez 3 patients tandis que chez 2 on a démontré également des anticorps IgA. Une réaction de P.K. positive a été observée chez des patients dont les sérums contenaient des anticorps IgA. Pendant la désensibilisation on a observé une apparition transitoire de macroglobulines capables de lier l'insuline131J. Après la désensibilisation on a constaté la persistance de la positivité aux réactions cutanées immédiates à l'insuline de porc et de boeuf. En même temps les réactions retardées et la réaction de P.K. à l'insuline de porc étaient interverties, bien que les mêmes réactions à l'insuline bovine restaient positives.
    Abstract: Resumen Cinco pacientes que padecían de alergia a la insulina han sido desensibilizados con insulina porcina según el método de Urbach y Gotlieb. El diagnóstico de alergia a la insulina ha sido puesto teniendo en cuenta las manifestaciones clínicas, el positivismo de las reacciones cutáneas, y, en 2 casos, las reacciones de Prausnitz-Küstner (P.K.). En 3 casos se ha obtenido desensibilización. La presencia de anticuerpos anti-insulina ha sido puesta en evidencia con el método inmunoautoradiográfico, empleando insulina131J. Antes de la desensibilización, la presencia de anticuerpos IgG ha sido hallada en 3 pacientes, mientras que en 2 han sido demostrados también anticuerpos IgA. Una reacción de P.K. positiva ha sido observada en pacientes cuyos sueros contenían anticuerpos IgA. Durante la desensibilización se ha observado aparición transitoria de macroglobulinas capaces de ligar la insulina131J. Al cabo de la desensibilización se ha notado la persistencia del positivismo a las respuestas cutáneas inmediatas a la insulina porcina y bovina. Al mismo tiempo, las respuestas retardadas y la reacción de P.K. a la insulina porcina cstaban invertidas, no obstante que las mismas reacciones a la insulina bovina hubieran quedado positivas.
    Notes: Riassunto Cinque pazienti con allergia all'insulina sono stati desensibilizzati con insulina suina secondo il metodo di Urbach e Gotlieb. La diagnosi di allergia all'insulina è stata posta sulla base delle manifestazioni cliniche, della positività delle reazioni cutanee e, in 2 casi, delle reazioni di Prausnitz-Küstner (P.K.). In 3 casi si è ottenuta una desensibilizzazione. La presenza di anticorpi anti-insulina è stata rivelata con il metodo immunoautoradiografico impiegando insulina131J. Prima della desensibilizzazione la presenza di anticorpi IgG è stata riscontrata in 3 pazienti mentre in 2 sono stati dimostrati anche anticorpi IgA. Una reazione di P.K. positiva è stata osservata in pazienti i cui sieri contenevano anticorpi IgA. Durante la desensibilizzazione si è osservata una comparsa transitoria di macroglobuline capaci di legare l'insulina131J. Dopo la desensibilizzazione si è riscontrata la persistenza della positività delle risposte cutanee immediate all'insulina suina e bovina. Al tempo stesso le risposte ritardate e la reazione di P.K. all'insulina suina erano invertite, sebbene le stesse reazioni all'insulina bovina rimanessero positive.
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  • 93
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    Diabetologia 4 (1968), S. 111-117 
    ISSN: 1432-0428
    Keywords: Insulin ; diabetes ; insulinase ; rat diaphragm ; glycogen synthesis ; RNA turnover ; cell culture ; anti-insulin serum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Peu de progrès conduisant à la compréhension du diabète en termes moléculaires ont été réalisés. La possibilité qu'il existe une modification dans la structure de l'insuline des diabétiques, aussi bien circulante que pancréatique, s'appuie sur trois arguments expérimentaux obtenus au laboratoire des auteurs. — La purification immunochimique de l'insuline circulante de diabétiques jeunes non traités par l'insuline a d'abord conduit à la constatation que cette insuline est relativement résistante à l'action réductrice et protéolytique d'une préparation d'insulinase musculaire. De plus, l'insuline pancréatique, isolée à partir de cinq pancréas diabétiques, s'est avérée d'activité biologique diminuée quant à son pouvoir d'augmenter la synthèse du glycogènein vivo et à sa capacité d'accélérer le “turnover” du R.N.A. en culture tissulaire. — La nature de cette „insuline anormale” et son rôle possible dans la physiopathologie du diabète sont examinés à la lumière de la nécessité de donner une définition spécifique de la modification moléculaire précise.
    Abstract: Zusammenfassung Unsere Kenntnisse über den Diabetes in molekularbiologischer Sicht haben kaum Fortschritte gemacht. Die Möglichkeit, daß das zirkulierende und das Pankreas-Insulin des Diabetikers strukturelle Unterschiede aufweisen, wird durch die Ergebnisse von drei verschiedenen Untersuchungsreihen gestützt, die im Laboratorium der Verfasser durchgeführt wurden. — Immunologisch gereinigtes zirkulierendes Insulin von Diabetikern, die noch kein Insulin erhalten hatten, erwies sich als recht widerstandsfähig gegenüber dem Abbau durch ein Insulinase-Rohextrakt aus Muskelgewebe. Aus den Bauchspeicheldrüsen von 5 Diabetikern gewonnenes Insulin zeigte sowohl in seiner Fähigkeit, die Glycogen-Synthesein vivo, als auch den Ribonucleinsäuren-Umsatz in der Gewebskultur zu stimulieren, eine herabgesetzte biologische Aktivität. — Bei der Diskussion der Natur dieses „abnormen” Insulins und seiner hypothetischen Rolle in der Physiopathologie des Diabetes ergibt sich besonders deutlich, wie dringend erforderlich eine genauere Klärung des in diesem Falle vorliegenden molekularen Umbaus ist.
    Notes: Summary Understanding of diabetes in molecular terms has advanced very little. The possibility that a structural difference exists in the circulating and pancreatic insulin moiety of diabetics is supported by three lines of evidence obtained in the authors' laboratory. — Immunologically purified circulating insulin from diabetic subjects untreated with insulin was noted to be relatively resistant to degradation by a crude muscle insulinase preparation. The pancreatic insulin of five diabetic pancreases was found to have a decreased biological activity in its ability to enhance glycogen synthesisin vivo and in its capacity to stimulate RNA turnover in tissue culture. — The nature of this “abnormal insulin” and its hypothetical role in the physiopathology of diabetes are discussed in the light of the need for a specific definition of the precise molecular change.
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  • 94
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    Diabetologia 4 (1968), S. 1-9 
    ISSN: 1432-0428
    Keywords: Human growth hormone ; Growth hormone ; Insulin ; Diabetes mellitus ; Experimental diabetes ; Acromegaly ; Pathogenesis of diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Il a été démontré récemment que l'hormone de croissance humaine (HGH) joue un rôle prééminent dans la régulation normale de la glycémie. De plus, il est bien connu que l'hormone de croissance peut créer un état semblable au diabète chez l'animal. Chez l'homme, l'injection de HGH ou l'hypersécrétion de l'hormone endogène dans l'acromégalie est suivie d'intolérance au glucose seulement dans 25% des cas. — Dans ce travail nous présentons des données qui mettent l'action dite diabétogène de HGH dans un contexte plus nuancé. Nous suggérons que HGH, bien que diminuant l'utilisation du glucose par les tissus périphériques, n'est pas une substance primairement diabétogène, car l'effet insulinotrope de l'hormone cause une hyperinsulinémie compensatrice, qui à son tour normalise la tolérance au glucose. HGH est diabétogène exclusivement chez les sujets prédiabétiques dont le pancréas est incapable de répondre à l'effet insulinotrope de l'hormone. Chez ces sujets, la diabétogénicité de HGH n'étant pas surmontée par une hyperinsulinémie compensatrice, la tolérance au glucose sera anormale. Ainsi, HGH peut être considérée comme unfacteur additif pour la pathogénèse du diabète sucré, la condition essentielle et primaire étant un état préexistant de prédiabète.
    Abstract: Zusammenfassung Wie kürzlich gezeigt wurde, spielt das menschliche Wachstumshormon (HGH) eine wichtige Rolle bei der Kontrolle der Blutzucker-Homöostase. Ferner ist schon lange bekannt, daß die Verabreichung von Wachstumshormon an Tiere zu einem diabetesähnlichen Zustand führen kann. Beim Menschen löst die Gabe der Substanz oder die Überproduktion des endogenen Hormons bei der Akromegalie nur in etwa 25 % der Fälle eine Glucosetoleranzstörung aus. — In dieser Arbeit werden Resultate beschrieben, die ein detaillierteres Bild der sogenannten diabetogenen Wirkung des HGH vermitteln. Wir möchten annehmen, daß das HGH, obwohl es den peripheren Glucoseverbraueh herabsetzt, kein primär diabetogener Faktor ist, da es über eine Insulin-mehrausschüttung zu einem Hyperinsulinismus führt, der eine normale Glucosetoleranz bewirkt. HGH zeigt Scine diabetogene Wirkung nur bei Prädiabetikern, deren Pankreas den stimulierenden Effekt des Hormons auf die Insulinausschüttung nicht beantworten kann. Bei diesen Personen kann eine Störung der Glucosetoleranz dadurch entstehen, daß die diabetogene Wirkung des HGH nicht durch einen kompensatorischen Hyperinsulinismus ausgeglichen wird. HGH kann daher als ein Zusatzfaktor bei der Diabetesentstehung angesehen werden, deren Hauptvorbedingung jedoch eine schon vorher bestehende prädiabetische Stoffwechselsituation darstellt.
    Notes: Summary Human growth hormone (HGH) has recently been shown to play a prominent role in the control of blood glucose homeostasis. Furthermore, it has long been known that administration of growth hormone in animals can induce a diabetes-like state. In human subjects, exogenous administration of HGH or hypersecretion of the endogenous hormone in acromegaly is accompanied by glucose intolerance in only about 25 per cent of the cases. — In this paper, data are presented which give a more diversified picture of the so-called diabetogenic action of HGH. It is suggested that HGH, although decreasing the peripheral utilization of glucose, is not a primary diabetogenic factor, since its insulinogenic action causes a compensatory hyperinsulinism, with normal glucose tolerance as the result. HGH is diabetogenic only in prediabetic subjects whose pancreas is unable to respond to the insulinogenic effect of the hormone. In such subjects, the diabetogenic action of HGH not being counterbalanced by a compensatory hyperinsulinism, glucose intolerance may result. Thus, HGH may be regarded as anadditional factor for the development of diabetes, the major prerequisite being a preëxisting prediabetic state.
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  • 95
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    Diabetologia 4 (1968), S. 281-285 
    ISSN: 1432-0428
    Keywords: Insulin ; radioimmunoassay ; bile ; bile acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'effet des acides biliaires sur le dosage radioimmunologique de l'insuline a été examiné et les résultats ont montré que les acides biliaires en concentrations physiologiques nuisent à la liaison de l'insuline avec le sérum anti-insulinique. La courbe de dilution de l'insuline immunoréaetive dans la bile de la vésicule biliaire porcine n'était pas parallèle à celle de l'insuline porcine standard. Après extraction de la bile porcine par du sérum antiinsulinique et après dosage de l'extrait, des taux d'insuline plus bas ont été trouvés. Les résultats suggèrent qu'une partie seulement de «l'insuline immunoreactive» de la bile de la vésicule biliaire représente de l'insuline véritable.
    Abstract: Zusammenfassung Die Wirkung von Gallensäuren auf die radio-immunologische Insulinbestimmung wurde untersucht. Aus den Resultaten geht hervor, daß Gallensäuren in physiologischen Konzentrationen zu einer Störung der Insulinbindung an Anti-Insulinserum führen. Die Verdünnungskurve von immunoreaktivem Insulin im Gallensaft aus Schweinegallenblasen verlief nicht parallel zur Standard-Eichkurve von Schweineinsulin. Nach Extraktion der Schweinegalle mit Anti-Insulinserum fanden sich im Extrakt niedrigere Insulinkonzentrationen. Die Ergebnisse deuten darauf hin, daß nur ein Teil des „immunoreaktiven Insulins” in der Blasengalle echtes Insulin ist.
    Notes: Summary The effect of bile acids on the radioimmunoassay of insulin has been investigated, and the results show that bile acids in physiological concentrations interfere with the binding of insulin by anti-insulin serum. The dilution curve of immunoreactive insulin in pig gall-bladder bile was not parallel to that of standard pig insulin. After extraction of pig bile with anti-insulin serum and assay of the extract, lower insulin levels were found. The results suggest that only a part of the “immunoreactive insulin” in gall-bladder bile is genuine insulin.
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  • 96
    ISSN: 1432-0428
    Keywords: Insulin ; 3′,5′-AMP phosphodiesterase ; glycogen metabolism ; lipolysis ; insulin secretion ; antilipolytic action of insulin ; glycogen synthesis and insulin ; cyclic adenosine 3′,5′-monophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'influence de l'insuline sur le métabolisme du glycogène hépatique et sur la lipolyse semble s'exercer par l'intermédiaire d'une diminution de la concentration de 3,′5′-AMP intracellulaire. Onamontré une diminution de la formation de 3′5′-AMP dans le tissu adipeux incubé avec de l'insuline. L'influence de l'insuline sur la dégradation du 3,′5′-AMP est étudiée. — L'activité de la 3,′5′-AMP-phos-phodiestérase (PDE) est diminuée dans le foie, le tissu adipeux et, de façon non-significative, dans le muscle strié des rats qui manquent d'insuline, c-à-d les rats rendus diabétiques par l'alloxane ou les rats privés de nourriture. L'injection intraveineuse d'une faible dose d'insuline (0.5 U/kg) ou la stimulation de la sécrétion d'insuline endogène par une injection de glucose provoquent une augmentation rapide de l'activité de la phosphodiestérase dans ces tissus. 15 min après l'injection d'insuline, l'activité de la phosphodiesterase du foie est augmentée. L'effet maximum est atteint après 30–45 min. L'activité de la phosphodiestérase rénale n'est pas diminuée dans le diabète alloxanique, l'injection d'insuline s'est avérée inefficace.In vitro, l'insuline cristalline a un effet activant sur la phosphodiestérase purifiée du coeur de boeuf. La concentration d'insuline requise pour doubler l'activité de l'enzyme est de l'ordre de 2 · 10−5 M. Le traitement avec actinomycin D empêche la stimulation par l'insuline de la PDE dans le foie. Ceci peut indiquer que l'action de l'insuline sur l'activité de la phosphodiestérase est essentiellement basée sur une synthèse accrue de l'enzyme. A cause de l'influence de la sécrétion d'insuline sur la concentration en 3,′5′-AMP du foie et du tissu adipeux, le métabolisme du glycogène et la lipolyse peuvent s'adapter rapidement à la prise de nourriture.
    Abstract: Zusammenfassung An der Steigerung der Glykogensynthese der Leber und der Verminderung der Lipolyse durch Insulin ist eine Abnahme der 3′,5′-AMP-Konzentration wesentlich beteiligt. Die 3′,5′-AMP-Bildung ist in Fettgewebe, das mit Insulin inkubiert wird, vermindert. Insulin beeinflußt jedoch auch den 3′,5′-AMP-Abbau. -Die 3′,5′-AMP-Phosphodiesterase (PDE)-Aktivität des Fettgewebes, der Leber und, in geringerem Grade, der Skeletmuskulatur ist im Insulinmangel vermindert, d.h. bei alloxandiabetischen oder hungernden Ratten. I.v. Injektion von 0,5 E/kg Insulin oder eine erhöhte Abgabe von Insulin aus dem Pankreas nach Glucoseinjektion führen in diesen Geweben zu einem raschen Anstieg der PDE-Aktivität. Dieser ist in der Leber schon 15 min nach Insulingabe nachweisbar und erreicht nach 30–45 min sein Maximum. In der Niere ist kein Einfluß von Insulin auf die PDE-Aktivität nachweisbar. — Aus Rinderherz isolierte PDE wirdin vitro durch Insulin aktiviert, jedoch werden2 · 10−5 M zur Verdopplung der Aktivität benötigt. Actinomycin D verhindert die Steigerung der Leber-PDE-Aktivität nach Insulininjektion. So kann die Wirkung des Hormons im wesentlichen auf eine gesteigerte PDE-Synthese zurückgeführt werden. — Durch diesen Einfluß der Insulininkretion auf die 3′,5′-AMP-Konzentration in Leber und Fettgewebe können Glykogenstoffwechsel und Lipolyse rasch an die Nahrungsaufnahme angepaßt werden.
    Notes: Summary Influence of insulin on liver glycogen metabolism and on lipolysis appears to be mediated by a decreased intracellular 3′,5′-AMP concentration. Reduced formation of 3′,5′-AMP had been shown in adipose tissue incubated with insulin. The influence of insulin on 3′,5′-AMP degradation has been investigated. — 3′,5′-AMP phosphodiesterase (PDE) activity was reduced in liver, adipose tissue and, insignificantly, in skeletal muscle of insulin deficient, i.e. alloxan diabetic or starved rats. I.V. injection of a low dose of insulin (0.5 U/kg) or stimulation of endogenous insulin secretion by injection of glucose led to a rapid increase of PDE activity in these tissues. 15 min after insulin injection liver PDE activity was increased. The maximal effect occurred after 30–45 min. Renal PDE activity was not decreased in alloxan diabetes, insulin injection has been found ineffective. —In vitro, there was an activating effect of crystalline insulin on PDE purified from beef heart. Insulin concentration required for duplication of enzyme activity was of the order of 2 · 10−5 M. Treatment with actinomycin D nearly prevented stimulation of liver PDE by insulin. This may indicate that the action of insulin on PDE activity is essentially based on an increased enzyme synthesis. — Owing to the influence of insulin secretion on liver and adipose tissue 3′,5′-AMP concentration, glycogen metabolism and lipolysis can be quickly adapted to food intake.
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  • 97
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    Diabetologia 4 (1968), S. 68-70 
    ISSN: 1432-0428
    Keywords: Insulin ; proinsulin ; biosynthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Après incubation de tranches de pancréas d'embryon de veau, la leucine-H3 est incorporée dans une fraction protéique qui semble avoir les propriétés d'une “proinsuline”. Cette fraction protéique est de taille supérieure à l'insuline, possède l'immunoréactivité propre à l'insuline, et après traitement limité par la trypsine elle est transformée en un peptide semblable à l'insuline.
    Abstract: Zusammenfassung Die Inkubierung von Dünnschnitten des fötalen Rinder-Pankreas in Gegenwart vom H3- Leucin ergab einen Einbau dieser Amminosäure in eine Eiweißfraktion, die die Eigenschaften eines, Pro-Insulins' aufwies. Das Molekulargewicht dieser Eiweißfraktion war größer als dasjenige des Insulins; sie besaß die Immunreaktivität des Insulins und konnte durch teilweisen Abbau mit Trypsin in ein insulinähnliches Peptid umgewandelt werden.
    Notes: Summary Incubation of fœtal bovine pancreas slices resulted in the incorporation of3H-leucine into a protein fraction which appeared to have the properties of a ‘proinsulin’. This protein fraction was larger in size than insulin, possessed the immunoreactivity of insulin and was converted by limited trypsin treatment to a peptide similar to insulin.
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  • 98
    ISSN: 1591-9528
    Keywords: Insulin ; Monosaccharide ; Hormones ; Mammals ; Amphibians ; Insulinsekretion ; Monosaccharide ; Hormone ; Säugetiere ; Amphibien
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Stimulierung der Insulinsekretion durch Monosaccharide und Hormone wurde mit der Technik der Inkubation von isolierten Pankreasstückchen untersucht. Der Insulingehalt der Inkubationsmedien und der Pankreasgewebe wurde mit der biologischen (Oxydation von14C-Glucose durch das epidydemale Fettgewebe der Ratte) und der radioimmunologischen Bestimmungsmethode mit Trennung des freien und gebundenen Insulins durch Amberlite ermittelt. Das Kaninchenpankreas reagierte auf Glucose, Fructose, Ribose, Xylose, STH und Sekretin mit gleichbleibender Insulinausschüttung, nicht dagegen auf Galaktose, D- und L-Arabinose und ACTH. Die Gewebe anderer Säugetiere (Hund und Kalb, nicht aber Ratten) und einer Amphibienart (Grasfrosch) zeigten eine übereinstimmende Insulinfreisetzung nach Gabe von Glucose, wobei die Säugetiere etwa 1%, das Amphibium etwa 10% des Insulingehalts abgaben. Das Froschpankreas wies in seiner Reaktion eine jahreszeitliche Abhängigkeit auf, indem es im Winter nicht, im Sommer am stärksten auf die Stimulationsreize ansprach.
    Notes: Summary The stimulation of insulin-secretion by monosaccharides and hormones was studied with the technique of incubation of isolated pieces of pancreas. The insulin content of the incubation medium and of the pancreatic tissue was measured using both biological (oxidation of 14-C-glucose by epidydimal fat tissue of rats) and radio-immunological methods (separation of free and bound insulin with amberlite). The rabbit pancreas was stimulated by glucose, fructose, ribose, xylose (with constant insulin release), STH, and secretin, but not by galactose,d- andl-arabinose, and ACTH. The pancreatic tissue of other mammals (dog and calf, not rats) and one amphibian species (gras frog) showed the same insulin release after glucose which was 1% by mammals and 10% by amphibian of the insulin content of the tissue. The reaction of the frog pancreas depended upon the time of the year. In summer it reacted strongly to stimulants but in the winter it did not.
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  • 99
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    Naunyn-Schmiedeberg's archives of pharmacology 260 (1968), S. 254-268 
    ISSN: 1432-1912
    Keywords: Bilirubin ; Glucuronates ; Insulin ; Liver ; Tolbutamide ; Bilirubin ; Glucuronidsynthese ; Insulin ; Leber ; Tolbutamid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Lebergewebe von Ratten, die mit Tolbutamid, mit anderen blutzuckerwirksamen Sulfonylharnstoffderivaten oder mit Insulin behandelt worden waren, bildet bei Inkubation in vitro mehr Bilirubinglucuronid als das Gewebe unbehandelter Kontrolltiere. Dieser Effekt wurde 2 Std nach der intraperitonealen Injektion der blutzuckersenkenden Stoffe nachgewiesen, er tritt dosisabhängig auf und ist mit der blutzuckersenkenden Wirkung gut korreliert. Ein dem Tolbutamid chemisch verwandtes, jedoch blutzuckerunwirksames Methylsulfonylharnstoffderivat hatte diese Wirkung nicht. Die Steigerung der Glucuronidsynthese ist dadurch bedingt, daß in der Leberzelle während einer Insulin- oder Sulfonylharnstoffhypoglykämie vermehrt aktivierte Glucuronsäure (UDPGA) für die Konjugation bereitgestellt wird. Die Aktivität des für die Konjugationsreaktion verantwortlichen Enzyms, der UDP-Glucuronyltransferase, war unter unseren Versuchsbedingungen nicht verändert. Es fanden sich keine Anhaltspunkte dafür, daß in der Insulin- oder Sulfonylharnstoffhypoglykämie die Bildung von UDPGA aus UDPG beschleunigt erfolgt. Die Aktivität der UDPG-Dehydrogenase war nicht verändert, auch Faktoren, die eine Bildung von UDPGA begünstigen könnten, wie ein erhöhter NAD+/NADH-Quotient und eine gesteigerte ATP-Konzentration im Gewebe, waren nach Tolbutamid nicht nachzuweisen.
    Notes: Summary Liver tissue of rats pretreated with tolbutamide, with other hypoglycaemic sulfonylurea compounds, or with insulin formed more bilirubinglucuronide when incubated in vitro than the tissue of untreated controls. The effect was present two hours after the blood sugar lowering agents had been injected intraperitoneally. It was dose-dependent and well correlated to the hypoglycaemic response. A methylated sulfonylurea compound, which is chemically closely related to tolbutamide but devoid of blood sugar lowering activity failed to show this effect. Glucuronide formation in hypoglycaemia induced by insulin or tolbutamide is increased as more activated glucuronic acid (UDPGA) is made available to the conjugation reaction. There was no change in the activity of the enzyme responsible for glucuronide synthesis, the UDP-glucuronyl-transferase, in our experiments. There was no indication that the formation of UDPGA from UDPG was accelerated by insulin or sulfonylureas. There was no change in the activity of the hepatic UDPG-dehydrogenase. Factors which could favour the formation of UDPGA such as an increased NAD+/NADH ratio or an elevated ATP concentration in the tissue were not present following tolbutamide.
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  • 100
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    Pflügers Archiv 301 (1968), S. 254-258 
    ISSN: 1432-2013
    Keywords: Insulin ; Potassium Deficiency ; Membrane Potential ; Rat Diaphragm ; Insulin ; Kaliummangel ; Membranpotential ; Rattenzwerchfell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An 102 Zellen des Zwerchfells von insgesamt 7 Ratten mit alimentärem Kaliummangel fanden wir unter dem Einfluß von Insulin (0,1 I.E./ml) eine Depolarisation um 11,2 mV, nämlich von −94,6 (s=±6,4) mV bei insgesamt 100 Zellen auf −83,4 (s=±6,8)mV (p 〈 0,001). Die Kaliumkonzentration in der Inkubationslösung betrug 4,7 (s=±0,29) mval/l. — Ferner steigt die bei kaliumverarmten Tieren erniedrigte intracelluläre Kaliumkonzentration unter Insulineinfluß von 107 (s=±12) mval/lH2O IZR auf 130 (s=±19,8) mval/lH2O IZR an (p〈0,05). Die Befunde sprechen dafür, daß Insulin bei kaliumverarmten Tieren einen Netto-Kaliumeinstrom bewirkt, der eine Abnahme des Membranpotentials zur Folge hat.
    Notes: Summary In 102 single muscle cells of 7 rats with alimentary potassium depletion we found under influence of insulin (0.1 I.U./ml) a depolarisation of 11.2 mV, i.e. from −94.6 (s=±6.4)mV (100 cells) to −83.4 (s=±6.8)mV (p〈0.001). The potassium concentration in the incubation medium was 4.7 (s=±0.29) mequ/l. — In addition we measured under influence of insulin (0.1 I.U./ml) an intracellular potassium concentration of 130 mval/lH2O IZR, which is probably higher than in potassium deficient animals without insulin (p〈0.05). These findings suggest that insulin produces a netto potassium influx in potassium deficient animals, which could explain the depolarisation.
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