Comparison of the effect of somatostatin and an analogue, SMS 201-995, on gastrin and insulin secretion from isolated perfused rat stomach and pancreas.

The effects of a somatostatin analogue, SMS 201-995, and somatostatin-14 on gastrin and insulin release from the isolated perfused rat stomach and pancreas were studied. Equipotent effects were observed on the inhibition of basal gastrin release from the stomach. SMS 201-995 was approximately 14 times less effective than somatostatin-14 (molar basis) in the pancreas. At a high glucose concentration (17.6 mM), neither the analogue nor the peptide inhibited insulin release, but at a glucose concentration of 8.8 mM, there was significant inhibition. In the presence of 10 mM arginine plus glucose at a concentration of either 8.8 or 17.6 mM, insulin secretion was reduced by both SMS 201-995 and somatostatin-14 to levels obtained with glucose alone. However, when gastric inhibitory polypeptide (10 ng/ml) in the presence of 8.8 mM glucose was used to stimulate insulin release, somatostatin-14 completely inhibited the insulinotropic action of gastric inhibitory polypeptide while SMS 201-995 was without effect. Studies with this analogue suggest that arginine and gastric inhibitory polypeptide stimulate insulin release via different mechanisms.