Activation of Somatostatin Receptor Subtype 2 Inhibits Insulin Secretion in the Isolated Perfused Human Pancreas

OBJECTIVES Five distinct somatostatin receptors (SSTRs) have been cloned, characterized, and designated SSTRs 1-5. The role of these receptors in B-cell signaling has not been well characterized. METHODS In the current study, the isolated perfused human pancreas model was used to determine the specific effect of 4 different somatostatin receptor agonists on insulin secretion. CONCLUSION We demonstrated that the SSTR 2 agonist and octreotide significantly suppressed insulin secretion. Furthermore, even during the immunoneutralization of endogenous intrapancreatic somatostatin, the SSTR 2 agonist was able to reverse the effect of somatostatin immunoneutralization by suppressing insulin secretion. These results demonstrate that activation of SSTR 2 suppresses insulin secretion in the isolated perfused human pancreas.