Human and rat amylin have no effects on insulin secretion in isolated rat pancreatic islets

Broderick, Carol L.; Brooke, G. S.; DiMarchi, Richard D.; Gold, Gerald

doi:10.1016/0006-291x(91)90628-k

Cited by 51 publications

(25 citation statements)

References 21 publications

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“…Instead our data agree with results showing no influence of IAPP on glucose-stimulated insulin secretion [16,17,30]. One possible explanation for the failure of hIAPP to inhibit the insulin response to i. v. glucose in our study might be that following the long-term and continuous influence of high concentrations of endogenous hIAPP, any effect of the peptide had vanished due to down regulation of receptors or effector mechanisms.…”

Section: Discussionsupporting

confidence: 75%

“…This would suggest it inhibits both insulin secretion and action and, consequently, if overexpressed in a prediabetic stage, could add to the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus. It has, however, also been claimed that IAPP does not impair insulin secretion [16,17] or insulin sensitivity [18]. Therefore, its physiological function is not yet established.…”

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confidence: 99%

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Transgenic overexpression of human islet amyloid polypeptide inhibits insulin secretion and glucose elimination after gastric glucose gavage in mice

et al. 1998

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Islet amyloid polypeptide (IAPP, also designated amylin) is a 37 amino acid polypeptide which is synthesized in islet beta cells and co-stored and co-released with insulin [1±6]. Exogenous treatment with the peptide inhibits insulin secretion in the perfused rat pancreas [7], in isolated rat islets [8,9] and in vivo in rats [10] and humans [11], and a specific IAPP antagonist increases insulin secretion from islets [12]. It has also been shown that IAPP inhibits glycogen formation in skeletal muscle [13] and induces insulin resistance in rats [14,15]. This would suggest it inhibits both insulin secretion and action and, consequently, if overexpressed in a prediabetic stage, could add to the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus. It has, however, also been claimed that IAPP does not impair insulin secretion [16,17] or insulin sensitivity [18]. Therefore, its physiological function is not yet established. In addition to its putative physiological actions, IAPP is also of interest in diabetes pathogenesis due to its ability to form fibrils, which are constituents of the islet amyloid characteristically accompanying Type II diabetes [19,20].To study the physiological function of IAPP as a circulating peptide, transgenic mice overexpressing Diabetologia (1998) Summary Islet amyloid polypeptide (IAPP) is synthesized in islet beta cells and has been implicated in diabetes pathogenesis because it can inhibit insulin secretion and action and form fibrils leading to islet amyloidosis. Its physiological function has, however, not been established. We therefore examined insulin secretion and glucose elimination after i. v. or gastric gavage of glucose in transgenic mice overexpressing human IAPP (hIAPP) resulting in considerably increased circulating IAPP concentrations. The insulin response to and the glucose elimination after i. v. glucose (1 g/kg) were not different in transgenic mice compared with wild type animals, neither in males nor in females. In contrast, the insulin response to gastric glucose (150 mg/mouse) was reduced and the glucose elimination was inhibited in both male and female transgenic mice. The area under the 30 min insulin curve (AUC insulin ) was 21 ± 2 nmol/l in 30 min in transgenic males (n = 24) vs 43 ± 3 nmol/l in 30 min in wild type males (n = 26; p < 0.001) and the respective areas under the glucose curve (AUC glucose ) were 1.90 ± 0.12 and 1.62 ± 0.09 mol/l in 120 min (p < 0.05). Similarly, in females, the AUC insulin was 17 ± 2 nmol/l in 30 min in transgenic mice vs 25 ± 3 nmol/l in 30 min in wild type mice (p < 0.05) and the respective AUC glucose was 1.62 ± 0.7 and 1.12 ± 0.07 mol/l in 120 min (p < 0.001). Hence, endogenous hIAPP inhibits insulin secretion and glucose elimination after gastric glucose gavage in both male and female mice, indicating that overexpression of hIAPP could be a diabetogenic factor, via effects on the intestinal tract or the gut-islet axis or both. [Diabetologia (1998

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Section: Discussionsupporting

confidence: 75%

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confidence: 99%

Transgenic overexpression of human islet amyloid polypeptide inhibits insulin secretion and glucose elimination after gastric glucose gavage in mice

et al. 1998

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“…In early studies, exogenous IAPP was used exclusively. Exogenous IAPP was found to have either an inhibitory [4] or a stimulatory [5] or no effect [6] on insulin release, and to have either inhibitory [7] or no effect [8] on peripheral insulin sensitivity. Some recent studies were performed in other study models, such as transgenic mice [9,10] and endogenous IAPP neutralizers [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Chronically administered islet amyloid polypeptide in rats serves as an adiposity inhibitor and regulates energy homeostasis

et al. 2005

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“…In the present studies amylin did not inhibit glucose-induced insulin secretion, but on the contrary appeared to stimulate it at the higher dose used. It is possible that a portal infusion of amylin produces a pancreatic response more similar to that seen in perfused pancreas preparations where amylin causes either no effect [29] or a stimulation [30] of insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

S15261 antagonises amylin‐induced impaired glucose tolerance

et al. 1995

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Amylin has been postulated to antagonise or inhibit the action of insulin in peripheral rat tissues and thus contribute to, or be responsible for, the development of insulin resistance. We have recently reported that S15261 is a compound capable of increasing insulin sensitivity in ageing insulin resistant rats. In order to assess whether S15261 had any effects on amylin induced insulin resistance we used a model where amylin causes an impairement in glucose tolerance in an acute manner, by means of an intraportal infusion of the hormone in normal rats. We report here that S15261 can antagonise this amylin-induced impaired glucose tolerance.

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Human and rat amylin have no effects on insulin secretion in isolated rat pancreatic islets

Cited by 51 publications

References 21 publications

Transgenic overexpression of human islet amyloid polypeptide inhibits insulin secretion and glucose elimination after gastric glucose gavage in mice

Transgenic overexpression of human islet amyloid polypeptide inhibits insulin secretion and glucose elimination after gastric glucose gavage in mice

Chronically administered islet amyloid polypeptide in rats serves as an adiposity inhibitor and regulates energy homeostasis

S15261 antagonises amylin‐induced impaired glucose tolerance

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