Somatostatin inhibits insulin release via SSTR2 in hamster clonal β-cells and pancreatic islets

Somatostatin (SST) inhibits pancreatic endocrine secretion. It is generally accepted that SSTR2 and SSTR5 mediate the inhibition of glucagon and insulin release; respectively. The present study was performed to test the hypothesis that SSTR2, but not SSTR5, mediates SST-induced inhibition of insulin release in hamster beta-cells. Both hamster clonal beta-cells HIT-T15 and pancreatic islets were used to test this hypothesis. Both SST and a nonpeptide SSTR2 agonist L-779,976 (1-100 nM) inhibited insulin release from HIT-T15 and islets in a concentration-dependent manner. In contrast, nonpeptide agonists for SSTR I, 3, 4 and 5 at the highest concentration studied (1 mu M) failed to inhibit insulin release. PRL-2903, a peptide SSTR2 antagonist (0.1-1 mu M), antagonized SST induced inhibition of insulin release in a concentration-dependent manner. Taken together, we conclude that, in hamster beta-cells, SST inhibits insulin release via SSTR2 but not SSTR5. (c) 2005 Elsevier B.V. All rights reserved.