Somatostatin, Pancreatic Polypeptide, Substance P, and Neurotensin: Cellular Distribution and Effects on Stimulated Insulin Secretion in the Mouse*

Somatostatin, pancreatic polypeptide (PP), substance P1 and neurotensin were investigated in mice with regard to their cellular localization in gut and pancreas and their effects on stimulated insulin secretion. Immunohistochemical demonstration of the different peptides revealed the following distribution. PP cells were confined to the pancreatic islets where they seemed to be in close association with the glucagon cells. They were especially abundant in the duodenal part of the pancreas. Somatostatin cells were found in pancreatic islets as well as throughout the gastrointestinal tract. In contrast to PP cells, somatostatin and glucagon cells were more numerous in the splenic part of the pancreas. Scattered endocrine cells displaying substance P immunoreactivity were found mainly in the duodenum, whereas neurotensin cells predominated in the jejuno-ileum. In addition, substance P immunoreactivity was demonstrated in nerves of the intestinal wall. Neither substance P cells nor neurotensin cells could be demonstrated in the pancreas. At two dose levels, the different peptides administered iv immediately before iv injection of half-maximal doses of glucose or carbachol produced the following effects. Somatostatin, PP, and a low dose level of substance P inhibited glucose-induced insulin release. At a higher dose level, the inhibiting effect of substance P was abolished. Neurotensin had no effect. Somatostatin inhibited insulin secretion induced by carbachol, whereas substance P and PP were without effect. Neurotensin potentiated the response to carbachol. The results suggest that caution should be exercised when interpreting the effects of the different peptides on stimulated insulin release, since their actions are dependent upon the nature of the stimulus.