ENTEROSTATIN - ITS ABILITY TO INHIBIT INSULIN-SECRETION AND TO DECREASE HIGH-FAT FOOD-INTAKE

Enterostatin is a peptide which has been found to decrease food intake with a specificity for the fat contained in the food. In this work we have investigated the effect of enterostatin (Val-Pro-Asp-Pro-Arg) an d its proteolytic fragments, des-arg-enterostatin (Val-Pro-Asp-Pro) an d the tripeptide Asp-Pro-Arg, on insulin secretion. It was found that enterostatin and des-arg-enterostatin inhibited insulin secretion from isolated rat islets by 55.3% (P < 0.05) and 53.6% (P < 0.05) at 1.6 X 10(-4) M concentration, while the tripeptide Asp-Pro-Arg at 1.6 x 10( -4) m concentration had no significant effect and increased insulin se cretion by 33.0%. Enterostatin at 200 ng after intraventricular admini stration was found to inhibit the intake of a high-fat diet by 45.0%, while des-arg-enterostatin (200 ng) had no effect, in agreement with p revious findings. The tripeptide Asp-Pro-Arg (200 ng) had no effect on the intake of a high-fat diet compared to saline injection. The abili ty of enterostatin to inhibit high-fat food intake and decrease insuli n secretion may be important for the prevention of obesity and type II diabetes, conditions linked through hyperinsulinemia.