Effect of leptin on insulin, glugacon and somatostatin secretion in the perfused rat pancreas

We have investigated the effect of rat leptin as well as the 22-56 fragment of this molecule on pancreatic hormone secretion in the perfused rat pancr eas. In pancreases from fed rats, leptin failed to alter the insulin secret ion elicited by glucose, arginine or tolbutamide, but inhibited the insulin response to both CCK-8 and carbachol, secretagogues known to act on the B- cell by increasing phospholipid turnover. This insulinostatic effect was al so observed with the 22-56 leptin fragment, In pancreases obtained from 24- hour fasted rats, no effect of leptin on carbachol-induced insulin output w as found, perhaps as a consequence of depressed B-cell phospholipid metabol ism. Leptin did not influence glucagon or somatostatin release. Our results do not support the concept of leptin as a major regulator of B-cell functi on. Leptin inhibition of carbachol-induced insulin output might reflect a r estraining effect of this peptide on the cholinergic stimulation of insulin release.