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Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity

✍ Scribed by Kieren J. Mather; Giancarlo Paradisi; Rosalind Leaming; Ginger Hook; Helmut O. Steinberg; Naomi Fineberg; Rochelle Hanley; Alain D. Baron

Publisher: John Wiley and Sons
Year: 2002
Tongue: English
Weight: 241 KB
Volume: 18
Category: Article
ISSN: 1520-7552
DOI: 10.1002/dmrr.263

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Background

Amylin is a peptide co‐secreted with insulin by pancreatic β‐cells. A role for amylin in the pathogenesis of type 2 diabetes mellitus (DM2) has been suggested by in vitro and in vivo studies indicating an effect of amylin to cause insulin resistance and/or inhibit insulin secretion.

Methods

We have determined the effect of endogenous amylin on insulin secretion and insulin action in humans by performing 4‐h hyperglycemic clamps during infusion of placebo or a specific amylin receptor antagonist (ARA) in paired, double‐blinded, crossover studies. We studied nine healthy lean, ten healthy obese (BMI>27) and ten obesity‐matched DM2 subjects.

Results

Infusion of ARA alone had no effect on basal insulin, glucose or glucose turnover in any group. Under combined hyperglycemia and ARA infusion, lean subjects displayed a 32% augmentation in insulin levels [AUC 33 565±3556 (placebo) to 44 562±1379 (ARA) pmol/l/min, p<0.01]. The concomitant increase in glucose disposal rate (GDR) was proportionate, indicating no change in insulin sensitivity (ISI 27.7±2.7 vs 27.3±2.1, p=NS). In obese subjects, basal insulin and the rise in insulin during the clamp were greater (AUC I 44% increase from 82 054±15 407 to 117 922±27 085, p<0.01), and also accompanied by a proportionate rise in GDR reflecting an unchanged insulin sensitivity (ISI 12.1±2.9 vs 10.8±3.0, p=NS). In lean and obese subjects, the C‐peptide response to hyperglycemia was also augmented by ARA (p=0.007). No effect of ARA on insulin secretion or action was observed in diabetic subjects.

Conclusions

The present data are consistent with an effect of endogenous amylin on the β‐cell to modulate and/or restrain insulin secretion, and indicate that endogenous amylin does not affect insulin action. These observations provide the first human evidence that amylin plays a role in the modulation of insulin secretion. Copyright © 2002 John Wiley & Sons, Ltd.

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