, Volume 193, Issue 1, pp 97-103

Glucose-dependency of the insulin stimulatory effect of glucagon-like peptide-1 (7–36) amide on the rat pancreas

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The glucose-dependent action of GLP-1 (7–36) amide (GLP-1) on insulin secretion was studied in isolated islets and in the perfused rat pancreas. In islet experiments in the presence of non-stimulatory glucose levels (<3 mmol/1) a GLP-1 concentration of 10 nmol/1 increased insulin secretion by 83%. However, higher GLP-1 concentrations (25 and 100 nmol/l) could not further enhance this effect (85 and 83%, respectively). The onset of the stimulatory action of a supramaximal GLP-1-load (25 nmol/l) was at a glucose level of 3 mmol/l. In the perfused pancreas, 25 nmol/l GLP-1 induced a strong insulin release at 5 mmol/l glucose, but under basal glucose (2.8 mmol/l) only a slight enhancement of insulin secretion occurred during the late phase (30 to 54 min) of perfusion (P<0.05). In conclusion, a slight but not dose-dependent stimulation of insulin secretion by supramaximal GLP-1 loads under basal glucose levels was found. The necessary GLP-1 concentrations to achieve this in vitro effect are beyond physiological or postprandial levels.