ENDOGENOUS SOMATOSTATIN-28 MODULATES POSTPRANDIAL INSULIN-SECRETION IMMUNONEUTRALIZATION STUDIES IN BABOONS

Somatostatin-28 (S-28), secreted into the circulation from enterocytes after food, and S-14, released mainly from gastric and pancreatic D c ells and enteric neurons, inhibit peripheral cellular functions. We hy pothesized that S-28 is a humoral regulator of pancreatic B cell funct ion during nutrient absorption. Consistent with this postulate, we obs erved in baboons a two to threefold increase in portal and peripheral levels of S-28 after meals, with minimal changes in S-14. We attempted to demonstrate a hormonal effect of these peptides by measuring their concentrations before and after infusing a somatostatin-specific mono clonal antibody (mAb) into baboons and comparing glucose, insulin, and glucagon-like peptide-1 levels before and for 4 h after intragastric nutrients during a control study and on 2 d after mAb administration ( days 1 and 2). Basal growth hormone (GH) and glucagon levels and param eters of insulin and glucose kinetics were also measured. During immun oneutralization, we found that (a) postprandial insulin levels were el evated on days 1 and 2; (b) GH levels rose immediately and were sustai ned for 28 h, while glucagon fell; (c) basal insulin levels were uncha nged on day 1 but were increased two to threefold on day 2, coincident with decreased insulin sensitivity; and (d) plasma glucose concentrat ions were similar to control values. We attribute the eventual rise in fasting levels of insulin to its enhanced secretion in compensation f or the heightened insulin resistance from increased GH action. Based o n the elevated postmeal insulin levels after mAb administration, we co nclude that S-28 participates in the enteroinsular axis as a decretin to regulate postprandial insulin secretion.