Inhibition of insulin release by intraduodenally infused enterostatin-VPDPR in rats

Enterostatin, an amino-terminal pentapeptide produced in the intestinal lumen after cleavage of pancreatic procolipase, has been shown to suppress fat intake in rats after intraduodenal infusion. In this study, female Sprague-Dawley rats fitted with a duodenal catheter were intestinally infused with enterostatin (Val-Pro-Asp-Pro-Arg, 11.3 and 22.6 nmol/kg/min) plus 20% Intralipid for 30 min. Plasma insulin levels were significantly reduced, whereas plasma glucose concentrations were not altered by enterostatin-VPDPR. The tripeptide Asp-Pro-Arg was also found to decrease the levels of plasma insulin. However, the pentapeptide with the sequence Val-Pro-Gly-Pro-Arg, des-Arg-enterostatin Val-Pro-Asp-Pro and the tripeptide Pro-Asp-Pro failed to cause the reduction of plasma insulin levels in rats following intestinal infusion of these peptides. Radiolabeled enterostatin ([3H]VPDPR) was identified in plasma by HPLC following intraduodenal infusion of the peptide, indicating that the appearance of an intact enterostatin-VPDPR in blood. It is concluded that intestinally administered enterostatin-VPDPR and its metabolites reduce plasma levels of insulin stimulated by Intralipid.