Interaction of glucagon-like peptide-1(7-36)amide and somatostatin-14 in RINm5F cells and in the perfused rat pancreas.
Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide], a new important incretin candidate, binds to specific high-affinity receptors on rat insulinoma-derived beta-cells (RINm5F). In the present study, the effect of somatostatin-14 on the GLP-1(7-36)amide-induced insulin release and cAMP generation in this cell line was investigated. Somatostatin did not decrease basal insulin release of RINm5F cells. The GLP-1(7-36)amide-induced insulin release was decreased concentration dependently by somatostatin. Somatostatin, 1 microM reduced the maximally GLP-1(7-36)amide-stimulated (0.1 microM) insulin release to basal insulin levels. The GLP-1(7-36)amide-induced cAMP production was significantly decreased by somatostatin in a concentration-dependent manner. The GLP-1(7-36)amide concentration causing half-maximal cAMP production was 2.98 +/- 1.56 nM. Somatostatin left the EC50 unaltered but decreased the maximal GLP-1(7-36)amide effect for 32% in the presence of 1 nM somatostatin and for 50% at 1 microM. In additional experiments, the interaction of both hormones was evaluated in the perfused pancreas as a nontumor model. Somatostatin (1 nM, 1 microM) inhibited the glucose-induced (6.7 mM) and GLP-1(7-36)amide-potentiated (0.05, 0.5, and 5 nM) insulin release dose dependently. The biphasic pattern of insulin release remained preserved. The GLP-1(7-36)amide-induced insulin release is potently inhibited by somatostatin-14. This effect was demonstrated in different model systems for beta-cell function studies. The present data allow the conclusion that the somatostatin action upon GLP-1(7-36)amide effects is at least partly related to regulation of intracellular cyclic nucleotides.
Göke
R
R
Department of Internal Medicine, Philipps University of Marburg, F.R.G.
Fehmann
H C
HC
Richter
G
G
Trautmann
M
M
Göke
B
B
D007516:Adenoma, Islet Cell / Q000473:pathology*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007328:Insulin / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C055453:glucagon-like peptide 1 (7-36)amide; D013004:Somatostatin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP