GLUCOSE-DEPENDENCY OF THE INSULIN STIMULATORY EFFECT OF GLUCAGON-LIKEPEPTIDE-1 (7-36) AMIDE ON THE RAT PANCREAS

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 pancr eas. In islet experiments in the presence of non-stimulatory glucose l evels (< 3 mmol/1) a GLP-1 concentration of 10 nmol/l increased insuli n secretion by 83%. However, higher GLP-1 concentrations (25 and 100 n mol/1) could not further enhance this effect (85 and 83%, respectively ). The onset of the stimulatory action of a supramaximal GLP-1-load (2 5 nmol/1) 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/1) only a slight enhancement of in sulin secretion occurred during the late phase (30 to 54 min) of perfu sion (P < 0.05). In conclusion, a slight but not dose-dependent stimul ation of insulin secretion by supramaximal GLP-1 loads under basal glu cose levels was found. The necessary GLP-1 concentrations to achieve t his in vitro effect are beyond physiological or postprandial levels.