LEPTIN INHIBITS INSULIN-SECRETION AND REDUCES INSULIN MESSENGER-RNA LEVELS IN RAT ISOLATED PANCREATIC-ISLETS

The ob gene product leptin over the concentration range 0.1-100nM demo nstrated a U-shaped dose-response inhibition of glucose-stimulated ins ulin secretion by rat pancreatic islets, Thus, leptin (1 and 10nM) pro duced a significant inhibition whereas 100nM was ineffective. The inhi bitory effect of leptin was glucose dependent, had a rapid onset and w as readily reversed upon removal of leptin. Sub-chronic exposure of is lets to leptin (10nM) reduced both insulin secretion and the level of insulin transcript, These findings support the hypothesis that excessi ve production of leptin by adipose tissue could play a role in the dev elopment of non-insulin dependent diabetes in obese subjects. (C) 1997 Academic Press.