This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanizawa, Y. Articles by Oka, Y. Search for Related Content PubMed PubMed Citation Articles by Tanizawa, Y. Articles by Oka, Y.

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.

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.

This article has been cited by other articles:

				R. K. Srivastava and A. Krishna Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi Reproduction, January 1, 2007; 133(1): 165 - 176. [Abstract] [Full Text] [PDF]

				J. Seufert Leptin Effects on Pancreatic {beta}-Cell Gene Expression and Function Diabetes, February 1, 2004; 53(90001): S152 - 158. [Abstract] [Full Text]

				C. Bjorbaek and B. B. Kahn Leptin Signaling in the Central Nervous System and the Periphery Recent Prog. Horm. Res., January 1, 2004; 59(1): 305 - 331. [Abstract] [Full Text]

				D. A. Zieba, M. Amstalden, M. N. Maciel, D. H. Keisler, N. Raver, A. Gertler, and G. L. Williams Divergent Effects of Leptin on Luteinizing Hormone and Insulin Secretion Are Dose Dependent Experimental Biology and Medicine, March 1, 2003; 228(3): 325 - 330. [Abstract] [Full Text] [PDF]

				R. B. CEDDIA, H. A. KOISTINEN, J. R. ZIERATH, and G. SWEENEY Analysis of paradoxical observations on the association between leptin and insulin resistance FASEB J, August 1, 2002; 16(10): 1163 - 1176. [Abstract] [Full Text] [PDF]

				M. Amstalden, M.R. Garcia, R.L. Stanko, S.E. Nizielski, C.D. Morrison, D.H. Keisler, and G.L. Williams Central Infusion of Recombinant Ovine Leptin Normalizes Plasma Insulin and Stimulates a Novel Hypersecretion of Luteinizing Hormone after Short-Term Fasting in Mature Beef Cows Biol Reprod, May 1, 2002; 66(5): 1555 - 1561. [Abstract] [Full Text]

				J. A. Cases, I. Gabriely, X. H. Ma, X. M. Yang, T. Michaeli, N. Fleischer, L. Rossetti, and N. Barzilai Physiological Increase in Plasma Leptin Markedly Inhibits Insulin Secretion In Vivo Diabetes, February 1, 2001; 50(2): 348 - 352. [Abstract] [Full Text]

				K. Takekoshi, K. Ishii, Y. Kawakami, K. Isobe, T. Nanmoku, and T. Nakai Ca2+ Mobilization, Tyrosine Hydroxylase Activity, and Signaling Mechanisms in Cultured Porcine Adrenal Medullary Chromaffin Cells: Effects of Leptin Endocrinology, January 1, 2001; 142(1): 290 - 298. [Abstract] [Full Text] [PDF]

				S. Matthaei, M. Stumvoll, M. Kellerer, and H.-U. Häring Pathophysiology and Pharmacological Treatment of Insulin Resistance Endocr. Rev., December 1, 2000; 21(6): 585 - 618. [Abstract] [Full Text]

				T. J. Kieffer and J. F. Habener The adipoinsular axis: effects of leptin on pancreatic beta -cells Am J Physiol Endocrinol Metab, January 1, 2000; 278(1): E1 - E14. [Abstract] [Full Text] [PDF]

				B. Ahren and P. J. Havel Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line (INS-1 cells) Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1999; 277(4): R959 - R966. [Abstract] [Full Text] [PDF]

				L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]

				J. Seufert, T. J. Kieffer, C. A. Leech, G. G. Holz, W. Moritz, C. Ricordi, and J. F. Habener Leptin Suppression of Insulin Secretion and Gene Expression in Human Pancreatic Islets: Implications for the Development of Adipogenic Diabetes Mellitus J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 670 - 676. [Abstract] [Full Text]

				A. Glasow, A. Haidan, U. Hilbers, M. Breidert, J. Gillespie, W. A. Scherbaum, G. P. Chrousos, and S. R. Bornstein Expression of Ob Receptor in Normal Human Adrenals: Differential Regulation of Adrenocortical and Adrenomedullary Function by Leptin J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4459 - 4466. [Abstract] [Full Text]

				A. Mizuno, T. Murakami, S. Otani, M. Kuwajima, and K. Shima Leptin Affects Pancreatic Endocrine Functions through the Sympathetic Nervous System Endocrinology, September 1, 1998; 139(9): 3863 - 3870. [Abstract] [Full Text] [PDF]

				V. Poitout, C. Rouault, M. Guerre-Millo, I. Briaud, and G. Reach Inhibition of Insulin Secretion by Leptin in Normal Rodent Islets of Langerhans Endocrinology, March 1, 1998; 139(3): 822 - 826. [Abstract] [Full Text] [PDF]