Interaction of Glucagon-Like Peptide- 1 (7–36)amide and Somatostatin-14 in RINm5F Cells and in the Perfused Rat Pancreas

Abstract

Glucagon-like peptide- l(7–36)amide [GLP- 1(7–36)amide], a new important incretin candidate, binds to specific high-affinity receptors on rat insulinoma-derived @-cells (RINmSF). In the present study, the effect of somatostatin- 14 on the GLP-l(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 μM reduced the maximally GLP- l(7–36)amide-stimulated (0.1 μM) insulin release to basal insulin levels. The GLP- 1 (7–36)amide-induced cAMP production was significantly decreased by somatostatin in a concentrationdependent manner. The GLP- l(7–36)amide concentration causing halfmaximal 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 μM. In additional experiments, the interaction of both hormones was evaluated in the perfused pancreas as a nontumor model. Somatostatin (1 nM, 1 μM) 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- l(7–36)amide-induced insulin release is potently inhibited by somatostatin- 14. This effect was demonstrated in different model systems for β-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.