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

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