A physiologic role for somatostatin 28 as a regulator of insulin secretion.

Abstract

Somatostatin 28 (S-28) is a peptide produced in the intestinal tract which rises in the circulation during nutrient absorption. We tested the hypothesis that S-28 regulates B-cell function by (a) studying the effects on insulin secretion of "physiologic" infusions of S-28 and (b) measuring insulin responses during elevated nutrient-stimulated endogenous S-28 levels. (a) Synthetic S-28 was infused on separate days into six healthy men at rates of 25 and 50 ng/kg per h which mimicked postprandial levels. Subjects were given a bolus of glucose (0.1 g/kg) after 120 min. Insulin responses during S-28 infusions were compared to a control study using a saline infusion in the same individuals. Glucose-stimulated insulin secretion was inhibited during the infusion of 50 ng/kg per h S-28 when compared to control (P < 0.05). (b) Insulin secretion during elevations of endogenous S-28 was studied in healthy men who received a bolus of 2.5 g arginine (n = 14) or 25 U of secretin (n = 8) 120 min after swallowing 50 g fat, or, on a separate day, an equivalent volume of water. S-28 levels rose significantly after fat ingestion but did not change after water. Arginine and secretin-stimulated insulin secretion was inhibited following ingestion of fat compared with intake of water (P < 0.05). Arginineenhanced glucagon secretion was not changed by fat ingestion. We conclude that elevations in plasma S-28 levels, occurring during the postprandial state, attenuate B-cell secretion and this peptide may be a physiologic modulator of nutrient-stimulated insulin release.

Endogenous somatostatin-28 modulates postprandial insulin secretion. Immunoneutralization studies in baboons.

“…Thus, neither S-14 nor its conversion product S-13 is likely to serve as a hormone outside the splanchnic bed. However, based on inhibition of insulin release by S-28 infused to achieve postprandial levels in humans (18,19), coupled with the present findings, a creditable case can be made for S-28 as a humoral signal to islet B cells. S-28 is a potent inhibitor of insulin release, both in vivo and in vitro (38)(39)(40)(41), with a high binding affinity for B cells (42,43).…”

“…Thus, we hypothesized that S-28 is a regulator of glucose metabolism during the postprandial state. In earlier studies, we showed that infusion of S-28 in humans inhibited both the secretion of insulin from pancreatic B cells and the products of pancreatic acinar cells (18,19). Although these results support a physiologic role for S-28, a more compelling approach is to prevent the peptide from accessing its receptors and, thereafter, evaluate any changes in the release of products from the putative target cell (20)(21)(22).…”

Suppression of Insulin Production and Secretion by a Decretin Hormone

“…Somatostatin-28 (SST-28) is a peptide derivative of the pro-somatostatin gene that is expressed widely, including in gastrointestinal cells and pancreatic islet cells. Islet somatostatin signaling is thought to be principally paracrine, rather than endocrine, and serum SST-28 concentrations increase post-prandially (D’Alessio et al, 1989; Strowski and Blake, 2008). Galanin is an orexigenic neuropeptide produced throughout the CNS and in peripheral neurons, and has been reported to inhibit insulin secretion (Fehmann et al, 1995).…”

Function and expression of somatostatin receptors of the endocrine pancreas

“…It has been postulated that the postabsorptive increase of SST secretion may provide a mechanism to prevent excessive glucagon secretion (D'Alessio et al, 1989;Klaff and Taborsky, Jr. 1987). However, the role of pancreatic SST in inhibiting glucagon secretion may be more relevant in the basal state, because anti-SST enhanced glucagon output from the perfused human pancreas only at low glucose concentrations (Brunicardi et al, 2001;Kleinman et al, 1994).…”