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  • 1
    ISSN: 1432-0428
    Keywords: Nonsuppressible insulin-like activity ; NSILA-carrier protein ; human serum ; perfused rat heart ; glucose uptake ; hormone binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human serum in a concentration of 10% in the perfusion medium failed to increase glucose uptake by the isolated perfused rat heart, indicating that nonsuppressible insulin-like activity (NSILA) in whole serum was inactive in this system. When NSILA-carrier protein was added to partially purified NSILA-S, its biological activity on the rat heart disappeared. In contrast, the action of insulin was not affected by the presence of NSILA-carrier protein. Binding of125I-labelled NSILA-S to rat heart was inhibited by NSILA-carrier protein.125I-labelled insulin binding was not inhibited. These results support the hypothesis that NSILA-S bound to serum carrier protein is a large molecular compound which does not readily diffuse out of the capillary bed and therefore does not exert insulin-like effects in vivo.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin ; NSILA-S ; adipocytes ; hypophysectomized rats ; insulin-receptor ; NSILA-S-receptor ; glucose metabolism ; glucose transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated fat cells from normal and hypophysectomized rats have been compared with respect to: 1) binding of insulin and NSILA-S, and 2) effects of these two hormones on glucose transport and metabolism. Although both insulin and NSILA levels were decreased in the serum of hypophysectomized rats, insulin binding was decreased to about 63% of normal, whereas NSILA-S binding remained unchanged. Basal lipogenesis was similar in adipocytes of normal and hypophysectomized rats, but was not stimulated by either insulin or NSILA-S. Similarly, neither of the two hormones stimulated the net gas exchange of “intact” fat pads from hypophysectomized rats. In striking contrast to these findings, 3-O-methylglucose transport in unstimulated fat cells of hypophysectomized rats proceeded at a maximal rate which was not further enhanced by insulin or NSILA-S. These results suggest that the lack of one or several hormones of the pituitary causes one or several enzyme deficiencies responsible for the limited rate of lipogenesis, which otherwiese would proceed at a very rapid rate because of unrestrained glucose transport.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 485-493 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary IGF I and IGF II are two insulin-like growth factors resembling insulin in many respects. They stem from a common precursor, act through receptors similar to the insulin receptor with which they cross-react. When administered in large amounts they produce hypoglycemia. Their major effects, however, are on replication and differentiation of cells of mesodermal origin. IGF I is the major growth promoting factor in vivo. The synthesis and secretion of IGF I by the liver depend on the growth hormone status, insulin and nutrition. In contrast to insulin, the IGFs circulate in blood bound to the carrier proteins. Their half-life in man is in the order of 16 h. IGF I deficiency results in dwarfism (pygmy, Laron dwarf, toy poodle) despite normal or elevated growth hormone secretion. The anabolic actions of insulin and of the IGFs appear to complement each other as shown in Figure 7.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Insulin ; NSILA ; adipocytes ; diabetic rats ; insulin-receptor ; NSILA-receptor ; glucose transport ; glucose metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated fat cells from normal and streptozotocin-diabetic rats were compared with respect to metabolic indices (glucose-uptake, 3-0-methylglucose efflux) with and without stimulation by insulin and nonsuppressible insulin-like activity (NSILA). In addition, binding studies were carried out with these two hormones. Basal14C-glucose oxidation and incorporation into lipids was decreased in diabetic cells and their response to insulin and NSILA was greatly reduced. Basal efflux of 3-0-methylglucose from diabetic cells was somewhat faster than from normal cells. The response to insulin and NSILA was less than in normal cells and it was delayed. The apparent number of insulin binding sites as well as their affinity for insulin was increased in diabetic cells. In contrast, the apparent number of binding sites for NSILA was decreased in diabetic cells and their affinity for NSILA was increased. In normal cells insulin enhanced binding of125I-NSILA more markedly than in diabetic cells. These findings show that the rate-limiting step of impaired glucose metabolism (oxidation and lipogenesis) in diabetic fat cells is beyond the interaction of the hormone with the receptor. They suggest that the apparent number of hormone receptors (insulin, NSILA) on the cell membrane is regulated individually for each binding site.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Lipolysis ; adipose tissue ; epinephrine ; ACTH ; glucagon ; insulin ; streptozotocin-diabetes ; membrane receptors ; hypersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adipose tissue from streptozotocin-diabetic rats exhibits half-maximal lipolytic responses (FFA, glycerol release, increase in tissue FFA) to epinephrine at hormone concentrations 5–10 times lower than those required for half-maximal stimulation of lipolysis in adipose tissue from normal rats. The lipolytic response to epinephrine also occurs more promptly and the antilipolytic effect of insulin in the presence of submaximal epinephrine concentrations is much less pronounced than in normal tissue. In contrast, diabetic adipose tissue is less responsive to ACTH and glucagon than normal tissue. Half-maximal lipolytic responses are elicited by similar dibutyryl cyclic AMP concentrations in both tissues. Insulin treatment of diabetic rats during 24 hrs restores the lipolytic response of their adipose tissue to epinephrine to nearly normal. Our findings point to an abnormality of diabetic adipose tissue possibly related to the hypersensitivity of catecholamines encountered in denervated organs which are adrenergically innervated. They are consistent with the present concept of different hormone discriminators on the fat cell membrane and offer a further explanation for increased FFA mobilization in the diabetic state.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 1. La glycémie, l'insuline immunoréactive et les activités insuliniques supprimable et non supprimable ont été mesurées chez des rats chez les quels une hyperglycémie avait été provoquée par le glucose ou le D-mannoheptulose. Une corrélation entre la glycémie et l'activité insulinique supprimable a été observée dans tous les groupes de rats à l'exception de ceux traités par le mannoheptulose. Ces résultats confirment l'hypothèse selon laquelle l'action hyperglycémiante du mannoheptulose est due à son pouvoir inhibiteur de la sécrétion d'insuline par les cellules B des îlots de Langerhans.-2. Bien que les valeurs des activités insuliniques immunoréactive et supprimable fussent semblables, la corrélation quantitative entre ces deux mesures ne s'est pas avérée satisfaisante.-3. L'activité insulinique non supprimable est restée la même dans tous les groupes de rats. Les fluctuations de l'activité insulinique supprimable ne se sont pas traduites par des fluctuations de la concentration de l'activité insulinique non supprimable.
    Abstract: Zusammenfassung 1. Blutglucose, immunoreaktives Insulin, hemmbare und nicht hemmbare Insulinaktivität (IA) wurden bei Ratten bestimmt, die mit Glucose oder D-Mannoheptulose hyperglykämisch gemacht wurden. Blutglucose und hemmbare IA korrelierten in allen Gruppen mit Ausnahme der mit Mannoheptulose behandelten Ratten. Diese Resultate bestätigen frühere Befunde und Hypothesen, wonach Mannoheptulose die Insulinsekretion derβ-Zellen der Inseln unterdrückt.-2. Obschon sich immunoreaktives Insulin und hemmbare IA in den verschiedenen Gruppen von Ratten ähnlich verhielten, ergab sich keine gute Korrelation zwischen diesen beiden Größen.-3. Die Konzentration der nicht hemmbaren IA war in allen Gruppen von Ratten ungefähr gleich. Die Veränderungen der hemmbaren IA spiegelten sich in der Konzentration der nichthemmbaren IA nicht wieder.
    Notes: Summary 1. Blood glucose, immunoreactive, insulin suppressible and non-suppressible insulin-like activities were determined in rats after the administration of glucose and D-mannoheptulose respectively. The latter caused a marked rise of the blood sugar concentration There was a correlation between blood sugar and suppressible insulin-like activity in all groups of rats except those injected with mannoheptulose. The results support the concept that mannoheptulose acts by inhibiting the release of insulin from theβ-cells of the islets.-2. Immunoreactive insulin roughly paralleled suppressible ILA, but the quantitative correlation between the two was not satisfactory.-3. Nonsuppressible ILA was approximately the same in all groups of rats. Changes in the level of suppressible ILA were not reflected in the concentration of non-suppressible ILA.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Insulin-like growth factor-I ; insulin-like growth factor-II ; Type 2 (non-insulin-dependent) diabetes mellitus ; insulin resistance ; triglyceride ; cholesterol ; lipoprotein(a)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients. We, therefore, investigated total and fractionated triglyceride and cholesterol levels, lipoprotein(a), non-esterified fatty acid, and apolipoprotein levels in eight Type 2 diabetic patients during five control, five treatment, and three wash-out days. They received a constant diet throughout and daily 2×120 Μg insulin-like growth factor-I/kg s.c. during the treatment period. Fasting total and VLDL-triglyceride, total and LDL-cholesterol control levels were (mean ± SD) 3.1±2.6, 1.3±1.0, 6.3±1.3, and 4.5±1.1 mmol/l and decreased to 1.6±0.8, 0.6±0.4, 5.0±1.0, and 3.5±1.1 mmol/l, respectively, on the last treatment day (p〈0.01). During therapy, fasting lipoprotein(a) levels and the postprandial area under the triglyceride curve decreased by 48±22 and 32±18% of control (p〈0.01), respectively. In conclusion, insulin-like growth factor-I lowered lipid levels in Type 2 diabetic patients directly or indirectly or both because of decreased glucose and insulin levels. Long-term trials would be of interest with respect to the cardiovascular risk in Type 2 diabetes and patients with hyperlipidaemia.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Adipose tissue of diabetic rats ; prolonged incubationin vitro ; glucose transport and metabolism ; fructose metabolism, insulin sensitivity ; lipolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le métabolisme glucidique du tissu adipeux diabétique après incubation pendant 16 h dans un tampon contenant du glucose et de l'albumine, avec et sans insuline a été examiné. Le métabolisme glucidique d' abord diminué s'élevait à des taux normaux lors de l'incubation. Puisque la phlorizine supprimait cet effet stimulateur de l'incubation la diffusion facilitée du glucose semble être en cause. La sensibilité à l'insuline était maintenue pendant l'incubation, mais elle n'augmentait pas. — La libération de glycérol ainsi que l'incorporation du glucose-U-14C dans la fraction glycéride-glycérol augmentaient au cours de l'incubation et, alors, étaient inhibées par l'insuline. La synthèse des acides gras à partir du glucose-U-14C augmentait également mais n'atteignait pas des valeurs normales. — Tandis que le transport du glucose limite le métabolisme du glucose dans le tissu adipeux normal, la phosphorylation devenait le facteur limitant après l'incubation prolongée. Un agent inhibiteur de la synthèse des protéines, la cycloheximide, inhibait la stimulation du métabolisme du glucose par l'incubation même, tandis que l'actinomycine D était sans effet.
    Abstract: Zusammenfassung Diabetisches Fettgewebe wurde während 16 Std in einem Puffer mit Albumin und Glucose mit und ohne Insulin inkubiert, und die resultierenden Stoffwechselveränderungen mit Glucose-U-14C während einer zweiten Inkubation gemessen. Der anfänglich verminderte Glucosestoffwechsel des diabetischen Gewebes normalisierte sich im Verlaufe der Vorinkubation. Da Phlorizin diesen Vorinkubationseffekt auf die Glucoseaufnähme hemmte, darf eine Steigerung der Aktivität des mobilen Carriers dafür verantwortlich gemacht werden. Die Insulinempfindlichkeit des Gewebes blieb während der verlängerten Inkubation erhalten, nahm aber nicht parallel zur basalen Glucoseaufnahme zu. — Die Glycerinabgabe und der Einbau von Glucose-U-14C in die Glycerid-Glycerol-Fraktion nahm während der Inkubation zu und beide wurden durch Insulin zum Teil gehemmt. Die Fettsäuresynthese aus Glucose-U-14C wurde gesteigert, normalisierte sich aber nicht vollständig. — Im Gegensatz zu normalem Gewebe wurde an Stelle des Transportes die Phosphorylierung der Glucose zum geschwindigkeitsbestimmenden Faktor des Glucosestoff-wechsels. Cycloheximid verminderte den Vorinkubationseffekt auf den Glucosestoffwechsel, während Actinomycin D ohne Wirkung war.
    Notes: Summary The metabolism of diabetic adipose tissue was studied after prolonged preïncubationin vitro (16 h) in a medium containing albumin and glucose with and without insulin. The initially decreased glucose uptake and metabolism of diabetic adipose tissue rose to normal levels during incubation. This increase was subject to inhibition by phlorizin, indicating that facilitated glucose diffusion was responsible. The tissue remained insulinsensitive during prolonged incubation. However, insulin sensitivity did not increase in the same way as basal glucose uptake. — Glycerol release and incorporation of glucose-U-14C into glyceride-glycerol increased during incubation, and both were inhibited to some extent by insulin. Fatty acid synthesis from glucose-U-14C increased during incubation but did not reach normal values. — Unlike tissues of fed rats, phosphorylation of glucose rather than transport became the rate-limiting step in glucose metabolism after prolonged incubationin vitro. Cycloheximide, but not actinomycin D, inhibited the preïncubation effect.
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  • 10
    ISSN: 1432-0428
    Keywords: Substrate oxidation ; energy expenditure ; lipolysis ; ketogenesis ; “dawn” phenomenon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27±4 years, BMI 21.8±1.7 kg/m2) were treated with NaCl 0.9% (saline) or IGF-I (8 Μg · kg−1 · h−1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg−1 · day−1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80% (p〈0.02) and C-peptide levels by 78% (p〈0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10±0.43 (saline) to 2.79±0.37 ml · 100ml−1 · min−1 (IGF-I) (p〈0.02). GH-pulse: 10 h after i.v. GH injection serum GH peaked at 40.9±7.4 ng/ml. GH did not influence circulating levels of total IGFI, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702±267 (saline) and 885±236 (IGF-I) to 963±215 (saline) (p〈0.05) and 1815±586 Μmol/l (IGF-I) (p〈0.02), respectively; after 5 h, 3-OH-butyrate rose from 242±234 (saline) and 340±280 (IGF-I) to 678±638 (saline) (p〈0.02) and 1115±578 Μmol/l (IGF-I) (p〈0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44±195 to 300±370 after 20 min (p〈0.03) and to 287±91 nmol · 100 ml−1 · min−1after 120 min (p〈0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.
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