DIRECT STIMULATION OF BASAL INSULIN-SECRETION BY PHYSIOLOGICAL CONCENTRATIONS OF LEPTIN IN PANCREATIC BETA-CELLS

We examined a possible mechanism underlying the link between obesity a nd hyperinsulinemia, focusing on leptin, a peptide released from adipo cytes which affects the satiety center in the brain. The leptin recept or isoforms, Ob-Ra and Ob-Rb, are present in the pancreatic beta cell line MIN6 and in rat pancreatic islets, based on RT-PCR. A 2 hr, but n ot a 30 min, incubation with 1 nM recombinant mouse leptin, the concen tration observed in obese subjects, stimulated basal (at 5 mM glucose) insulin secretion by approximately 40 % in both MIN6 and rat islets. Stimulatory effects were not observed without glucose or when the incu bation medium containing 1 nM leptin had been preincubated with the im mobilized leptin antibody. In contrast to the stimulatory effects on b asal insulin secretion at 1 nM, the maximally stimulated insulin secre tion at 25 mM glucose was not significantly changed by 1 nM leptin in isolated rat islets. In addition, 10 and 100 nM leptin exerted small b ut significant inhibitory effects on 16.7 mM glucose-stimulated insuli n secretion. Thus, leptin acts directly on pancreatic beta cells, and stimulation of basal insulin secretion by physiological concentrations of leptin may account in part for the fasting hyperinsulinemia observ ed in obese subjects.