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Direct Stimulation of Basal Insulin Secretion by Physiological Concentrations of Leptin in Pancreatic ß Cells

Third Department of Internal Medicine (Y.T., S.O., Y.O.), Yamaguchi University School of Medicine, Ube Yamaguchi 755, Japan; Third Department of Internal Medicine (H.I., T.A.), Faculty of Medicine, University of Tokyo, Hongo, Tokyo 113, Japan; First Department of Physiology (T.Y.), Kagoshima University School of Medicine, Sakuragaoka, Kagoshima 890, Japan

Address all correspondence and requests for reprints to: Dr. Yoshitomo Oka, Yamaguchi University School of Medicine, Third Department of Internal Medicine, 1144 Kogushi, Yamaguchi, Ube 755, Japan.

	Abstract

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We examined a possible mechanism underlying the link between obesity and hyperinsulinemia, focusing on leptin, a peptide released from adipocytes which affects the satiety center in the brain. The leptin receptor isoforms, Ob-Ra and Ob-Rb, are present in the pancreatic ß cell line MIN6 and in rat pancreatic islets, based on RT-PCR. A 2 hr, but not a 30 min, incubation with 1 nM recombinant mouse leptin, the concentration 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 incubation medium containing 1 nM leptin had been preincubated with the immobilized leptin antibody. In contrast to the stimulatory effects on basal insulin secretion at 1 nM, the maximally stimulated insulin secretion 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 but significant inhibitory effects on 16.7 mM glucose-stimulated insulin secretion. Thus, leptin acts directly on pancreatic ß cells, and stimulation of basal insulin secretion by physiological concentrations of leptin may account in part for the fasting hyperinsulinemia observed in obese subjects.

Received May 14, 1997.

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