Effect of enterostatin on insulin, glucagon, and somatostatin secretion in the perfused rat pancreas

Enterostatin is a pentapeptide generated by trypic digestion of procolipase in the small intestine. Both peripheral and central administration of this peptide to rats has been shown to reduce food intake, this reduction being due to specific suppression of fat intake, In perifused pancreatic rat islets, enterostatin has been shown to inhibit the insulin response to a high glucose concentration. In the present study, we have investigated the effect of exogenous enterostatin on insulin, glucagon, and somatostatin secretion by the isolated perfused rat pancreas. Enterostatin, at 100 nmol/l, inhibited the insulin response to 9 mmol/l glucose (by 70%), 0.1 mmol/l tolbutamide (by 40%), and 5 mmol/l arginine (by 70%), Enterostatin had no effect on glucagon and somatostatin release at a maintained glucose level (5.5 mmol/l) or in response to 5 mmol/l arginine, Finally, preinfusion of the rat pancreas with a high enterostatin concentration (500 nmol/l) did not alter the insulin response to glucose, an observation that would rule out a toxic effect of this peptide on the beta-cell. In summary, in the perfused rat pancreas, enterostatin, at putatively physiological concentrations, inhibits insulin secretion without affecting glucagon or somatostatin output, thus pointing to a direct effect of enterostatin on the beta-cell and not through an alpha-cell or delta-cell paracrine effect, Because enterostatin is generated in the small intestine after feeding, it might play a role in the enteroinsular axis as an anti-incretin agent.