Peptide receptor antagonists in the study of insulin and glucagon secretion in mice

Peptide antagonists might be useful tools in elucidating a potential role for neuropeptides in islet hormone secretion. We therefore investigated the effects of three different peptide receptor antagonists on insulin and glucagon secretion in vivo in mice. The gastrin-releasing peptide (GRP) antagonist N-acetyl GRP-(20-26) amide (P less than 0.01) and the vasoactive intestinal polypeptide (VIP) antagonist [4Cl-D-Phe 6,Leu17] VIP (P less than 0.001) specifically inhibited insulin secretion induced by GRP and VIP, respectively. Furthermore, N-acetyl GRP-(20-26) amide specifically inhibited GRP-stimulated glucagon secretion (P less than 0.01) and the cholecystokinin (CCK) antagonist L-364,718 inhibited CCK-8-mediated insulin and glucagon secretion (P less than 0.001). However, neither of these three antagonists affected insulin or glucagon secretion stimulated by autonomic nerve activation (induced by 2-deoxy-glucose (2-DG)). We conclude that these peptide antagonists can be used in studies on the physiological involvement of GRP, VIP and CCK in islet hormone secretion. Furthermore, neither GRP or CCK seems involved in the insulin and glucagon response to 2-DG in the mouse.