Do the actions of glucagon-like peptide-1 on gastric emptying, appetite, and food intake involve release of amylin in humans?

J Clin Endocrinol Metab. 2010 May;95(5):2367-75. doi: 10.1210/jc.2009-2133. Epub 2010 Mar 1.

Abstract

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 9 mm, 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.

Trial registration: ClinicalTrials.gov NCT00876231.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyloid / blood
  • Amyloid / metabolism*
  • Amyloid / pharmacology
  • Appetite / drug effects*
  • Appetite / physiology
  • Body Mass Index
  • C-Peptide / blood
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Gastric Emptying / drug effects*
  • Gastric Emptying / physiology
  • Glucagon / antagonists & inhibitors
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Islet Amyloid Polypeptide
  • Reference Values
  • Single-Blind Method

Substances

  • Amyloid
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Islet Amyloid Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • pramlintide

Associated data

  • ClinicalTrials.gov/NCT00876231