Do the Actions of Glucagon-Like Peptide-1 on Gastric Emptying, Appetite, and Food Intake Involve Release of Amylin in Humans?

Objective: Amylin, cosecreted with insulin, has like glucagon-like peptide-1 (GLP-1) been reported to inhibit glucagon secretion, delay gastric emptying, and reduce appetite and food intake. We investigated whether the effects of GLP-1 on gastric emptying, appetite, and food intake are mediated directly or indirectly via release of amylin. Design: Eleven C-peptide and amylin-negative patients with type 1 diabetes mellitus (T1DM) and 12 matched healthy controls participated in a placebo-controlled, randomized, single-blinded, crossover study. With glucose clamped between 6 and 9mM, near-physiological infusions of GLP-1, human amylin, pramlintide, or saline were given for 270 min during and after a fixed meal. Gastric emptying was measured using paracetamol, appetite using visual analog scales, and food intake during a subsequent ad libitum meal (at 240 min). Results: In T1DM, gastric emptying, food intake, and appetite were reduced equally during low GLP-1 and amylin infusion compared with the saline infusion (P < 0.05). The controls showed stronger suppression of gastric emptying (P < 0.0001) and food intake (P < 0.01) with GLP-1 compared to amylin. Postprandial glucagon responses were reduced in controls and T1DM during GLP-1 and amylin infusions (P < 0.05). Amylin and pramlintide infusion had similar effects. Conclusions: GLP-1 exerts its effect on gastric emptying, appetite, food intake, and glucagon secretion directly, although secretion of amylin may contribute to some of these effects in healthy control subjects. (J Clin Endocrinol Metab 95: 2367-2375, 2010)