Colocalization of calcitonin gene-related peptide and somatostatin in pancreatic islet cells and inhibition of insulin secretion by calcitonin gene-related peptide in the rat

Calcitonin gene-related peptide (CGRP)-and somatostatin (SRlF)-containing cells were identified by immunocytochemical techniques in pancreatic islet cells of the rat. CGRP-containing cells were found primarily in the peripheral portion of the pancreatic islets. In addition, CGRP-containing cells also contained somatostatin, which identifies the islet CGRP-containing cells as D cells. In the present study, we also tested the effect of CGRP on gastrin-releasing peptide (GRP; 10^-9M)-or cholecystokinin (CCK-8, 10^-9M)-stimulated release of insulin from isolated rat islets in vitro. At concentrations of 10^-8-10^-11M, CGRP inhibited GRP-and CCK-8-stimulated release of insulin significantly when compared with GRP or CCK-8 alone. At the lowest concentration of CGRP (10^-11M), the inhibitory effect of CGRP on CCK-8-stimulated release of insulin was statistically significant (p < 0.05) and exceptionally potent (65-90% inhibition). We have also found that CGRP does not stimulate the release of SRIF from isolated islet cells. These findings suggest that CGRP may play a regulatory role in the release of insulin.