Library

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 1432-0428
    Keywords: Tritiated insulin ; subcutaneous insulin injections ; chemical analysis of injection site ; absorption kinetics ; local insulin degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The absorption of subcutaneously injected insulin was examined by injecting semisynthetic [3H] insulin in anaesthetized pigs and subsequently analysing the tissue excised from the injection site. Contrary to previously accepted views, a significant proportion of insulin was degraded at the injection site. The disappearance of intact [3H] insulin from the injection site followed a monoexponential function with a half-time of 59 min.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-0428
    Keywords: Exercise ; tritiated insulin ; subcutaneous insulin injections ; exercise-induced hypoglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies in man and pancreatectomized dogs have indicated that alterations of the pharmacokinetics of subcutaneously injected insulin during physical activity may contribute to exercise-induced hypoglycaemia in insulin-treated diabetic patients. We have directly measured the appearance of subcutaneously injected insulin in the circulation and assessed its distribution to different tissues using a recently developed semisynthetic homogeneous [3H]insulin as a tracer. Following subcutaneous injection in rats of [3H]insulin in amounts insufficient to exert significant biological activity in intact animals, circulating levels of exogenous insulin were measured as plasma radioactivity co-migrating with insulin during gel filtration chromatography. Strenuous treadmill running accelerated the mobilization of subcutaneously injected [3H] insulin and resulted in a significant elevation of circulating levels of exogenous insulin early during exercise, followed by decreased levels in the post-exercise period. In addition, exercise induced a redistribution of 3H radioactivity in tissues, mainly increasing that found in skeletal muscle. This direct demonstration of altered pharmacokinetics of subcutaneously injected insulin during exercise provides, at least in part, a mechanism for the exercise-induced hypoglycemia seen following insulin injections in animals and during insulin treatment in man.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 34 (1991), S. 202-203 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-0428
    Keywords: Keywords Intracerebroventricular ; neuropeptide Y ; hypothalamo-pituitary adrenal axis ; insulin ; proinsulin ; vagus nerve ; glucose utilisation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4–6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous system. [Diabetologia (1997) 40: 1269–1277]
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 34 (1991), S. 767-778 
    ISSN: 1432-0428
    Keywords: Preproinsulin ; proinsulin ; insulin ; C-peptide ; biosynthesis ; precursor processing ; protein trafficking ; protein degradation ; pancreatic Beta cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin is both produced and degraded within the pancreatic Beta cell. Production involves the synthesis of the initial insulin precursor preproinsulin, which is converted to proinsulin shortly after (or during) translocation into the lumen of the rough endoplasmic reticulum. Proinsulin is then transported to the trans-cisternae of the Golgi complex where it is directed towards nascent secretory granules. Conversion of proinsulin to insulin and C-peptide arises within secretory granules, and is dependent upon their acidification. Granule contents are discharged by exocytosis in response to an appropriate stimulus. This represents the regulated secretory pathway to which more than 99% of proinsulin is directed in Beta cells of a healthy individual. An alternative route also exists in the Beta cell, the constitutive secretory pathway. It involves the rapid transfer of products from the Golgi complex to the plasma membrane for immediate release, with, it is supposed, little occasion for prohormone conversion. Even if delivered appropriately to secretory granules, not all insulin is released; some is degraded by fusion of granules with lysosomes (crinophagy). Each event in the molecular lifestyles of insulin and its precursors in the Beta cell will be seen to be governed by their own discrete functional domains. The identification and characterisation of these protein domains will help elucidate the steps responsible for delivery of proinsulin to secretory granules and conversion to insulin. Understanding the molecular mechanism of these steps may, in turn, help to explain defective insulin production in certain disease states including diabetes mellitus.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. S65 
    ISSN: 1432-0428
    Keywords: Proinsulin ; conversion ; conversion intermediates ; insulin ; beta cell ; secretory pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Proinsulin is converted to insulin in betacell granules. Conversion involves endoproteolytic cleavage at the two pairs of basic residues linking the insulin A- and B-chains to C-peptide. The sequence of events leading to complete conversion differs from one proinsulin species to the next. In man, the structure of the proinsulin molecule is such as to favour cleavage at the B-chain/C-peptide junction leading to the generation of des-31,32 split proinsulin as the predominant, naturally occurring conversion intermediate. Under normal circumstances, proinsulin conversion is largely completed before secretion, and neither the intact prohormone nor conversion intermediates are thus encountered in large quantities in the circulation. In some pathological situations, including non-insulin-dependent diabetes, insulinoma and familial hyperproinsulinaemia, unusually high ratios of des-31,32 split proinsulin and/or proinsulin to insulin have been reported. As we understand the biochemistry of proinsulin conversion in increasingly fine molecular detail, it should become possible to make use of such unusual ratios to provide insight into lesions underlying altered beta-cell function in disease states.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 40 (1997), S. B33 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-0428
    Keywords: Keywords GFP ; insulin ; regulated secretory pathway ; secretory granules ; secretory alkaline phosphatase.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Sorting of proinsulin to the regulated secretory pathway of pancreatic beta cells and retention of insulin in dense-core granules of this pathway is remarkably efficient. To monitor the specificity of these events, the secretion of two exogenous secretory proteins not known to carry information for sorting or retention in the regulated pathway was investigated in INS-1 cells. Methods. SEGFP, a fusion protein consisting of a signal peptide N-terminal to EGFP (mutant green fluorescent protein with enhanced fluorescence) and secreted alkaline phosphatase (SEAP) were expressed in INS-1 cells by transfection and by infection with recombinant adenovirus, respectively. Secretion of SEGFP was monitored by quantitative western blotting and that of SEAP by its activity. Results. Secreted alkaline phosphatase showed high basal secretion (6.6 % total) but only modest (3.6-fold) stimulation of secretion by secretagogues, in keeping with secretion largely through the constitutive pathway. By contrast SEGFP had a secretory pattern similar to insulin, with low basal secretion (0.8 % total) and 16-fold stimulation by secretagogues. Granular localization of SEGFP was confirmed by high resolution electron microscopy immunocytochemistry. Pulse-chase experiments indicated retention of SEGFP in granules at least 24 h after synthesis. The secretory SEGFP, but not cytosolic EGFP, formed disulphide-linked oligomers. This could be implicated in its regulated secretion. Conclusion/interpretation. These data indicate that in INS-1 cells SEGFP, but not SEAP, is unexpectedly handled as a regulated secretory protein and stored along with insulin in granules. This raises questions about the specificity and mechanism of the sorting of proteins to granules in INS-1 cells or their retention therein or both. [Diabetologia (2000) 43: 1157–1164]
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1432-0428
    Keywords: Hyperinsulinaemic glucose clamp ; skeletal muscle ; liver ; insulin receptors ; tyrosine kinase ; insulin resistance ; β-subunit C-terminus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied autophosphorylation and tyrosine kinase activity of the insulin receptor purified from liver and muscle of fasted rats before and after infusion of insulin (100 mU/h) during a 2.5 h glucose clamp. Recovery of insulin receptors and insulin binding to the solubilised receptors was unaffected by the glucose clamp. Autophosphorylation of the insulin receptor β subunit was increased in liver receptors prepared from rats at the end of the glucose clamp compared to rats in the basal state both in the absence of insulin in vitro (109% increase, p〈0.001) and after in vitro stimulation with 10−7 mol/l insulin (clamped vs fasted; 96% increase, p〈0.001). Insulin (10−7 mol/l) stimulated autophosphorylation was also increased in muscle receptor preparations from clamped rats compared with rats in the basal state (58% increase, p〈0.05). In both liver and muscle receptors, the clamp increased the amount of [32P]-phosphate incorporated into the β subunit without changing the sensitivity of the insulin stimulation. HPLC analysis of the tryptic phosphopeptides derived from the β subunit after insulin stimulated autophosphorylation of liver receptors revealed an increase of 32P in all phosphorylation sites without any change in the overall pattern. Tyrosine kinase activity of liver and muscle insulin receptors from clamped rats was also increased approximately twofold (p〈0.05) when analysed using a synthetic substrate (poly Glu4 Tyr1). Our results support the notion that the insulin receptor exists in an active and inactive form, and that elevated plasma insulin concentrations increases the proportion of active receptors.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...