Glucose-dependency of the insulin stimulatory effect of glucagon-like peptide-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 pancreas. In islet experiments in the presence of non-stimulatory glucose levels (< 3 mmol/l) a GLP-1 concentration of 10 nmol/l 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.
Department of Internal Medicine, Philipps University of Marburg, Germany.
R
R
Göke
B
B
Wagner
H C
HC
Fehmann
B
B
Göke
D000577:Amides; D000818:Animals; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D000577:Amides; D007328:Insulin; D010446:Peptide Fragments; C061970:glucagon-like peptide 1 (7-36); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose