Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line (INS-1 cells)

Abstract

The effect of leptin on insulin secretion is controversial due to conflicting results in the literature. In the present study, we incubated insulin-producing rat insulinoma INS-1 cells for 60 min and examined the effects of recombinant murine leptin (20 nmol/1). We found that leptin (0.1- 100 nmol/1) did not affect the insulin response to glucose (1-20 mmol/1). However, when cells were incubated with agents that increase the intracellular content of cAMP, i.e., glucagon-like peptide-1 (100 nmol/1), pituitary adenylate cyc]ase activating polypeptide (100 nmol/1), forskolin (2.5 μmol/1), dibutyryl-cAMP (1 mmol/1), or 3-isobutyl-1-methylxanthine (100 μmol/1), leptin significantly reduced insulin secretion (by 34-58%, P < 0.05-0.001). In contrast, when insulin secretion was stimulated by the cholinergic agonist carbachol (100 μmol/1) or the phorbol ester 12-O- tetradecanoylphorbol 13-acetate (1 μmol/1), both of which activate protein kinase C, leptin was without effect. We conclude that leptin inhibits insulin secretion from INS-1 cells under conditions in which intracellular cAMP is increased. This suggests that the cAMP-protein kinase A signal transduction pathway is a target for leptin to inhibit insulin secretion in insulin- producing cells.