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Science 15 November 1996:
Vol. 274. no. 5290, pp. 1185 - 1188
DOI: 10.1126/science.274.5290.1185
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Reports

Modulation of Insulin Activities by Leptin

Batya Cohen, Daniela Novick, Menachem Rubinstein *

Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R. Variants of OB-R are found in other tissues, but their function is unknown. Here, an OB-R variant was found in human hepatic cells. Exposure of these cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals.

Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
*   To whom correspondence should be addressed. E-mail: lvrub{at}weizmann.weizmann.ac.il

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   Abstract »    Full Text »    PDF »
Plasma Leptin Levels : Interaction of Obesity With a Common Variant of Insulin Receptor Substrate-1.
F. Krempler, E. Hell, C. Winkler, D. Breban, and W. Patsch (1998)
Arterioscler. Thromb. Vasc. Biol. 18, 1686-1690
   Abstract »    Full Text »    PDF »
Insulin occludes leptin activation of ATP-sensitive K+ channels in rat CRI-G1 insulin secreting cells.
J Harvey and M L J Ashford (1998)
J. Physiol. 511, 695-706
   Abstract »    Full Text »    PDF »
Leptin Affects Pancreatic Endocrine Functions through the Sympathetic Nervous System.
A. Mizuno, T. Murakami, S. Otani, M. Kuwajima, and K. Shima (1998)
Endocrinology 139, 3863-3870
   Abstract »    Full Text »    PDF »
Understanding Adipocyte Differentiation.
F. M. GREGOIRE, C. M. SMAS, and H. S. SUL (1998)
Physiol Rev 78, 783-809
   Abstract »    Full Text »    PDF »
Role of tyrosine phosphorylation in leptin activation of ATP-sensitive K+ channels in the rat insulinoma cell line CRI-G1.
J Harvey and M L J Ashford (1998)
J. Physiol. 510, 47-61
   Abstract »    Full Text »    PDF »
Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting.
A. Kaibara, A. Moshyedi, T. Auffenberg, A. Abouhamze, E. M. Copeland III, S. Kalra, and L. L. Moldawer (1998)
Am J Physiol Regulatory Integrative Comp Physiol 274, R1518-R1525
   Abstract »    Full Text »    PDF »
Lack of Effect of Leptin on Glucose Transport, Lipoprotein Lipase, and Insulin Action in Adipose and Muscle Cells.
S. Ranganathan, T. P. Ciaraldi, R. R. Henry, S. Mudaliar, and P. A. Kern (1998)
Endocrinology 139, 2509-2513
   Abstract »    Full Text »    PDF »
Multihormonal Control of ob Gene Expression and Leptin Secretion from Cultured Human Visceral Adipose Tissue: Increased Responsiveness to Glucocorticoids in Obesity.
C. M. Halleux, I. Servais, B. A. Reul, R. Detry, and S. M. Brichard (1998)
J. Clin. Endocrinol. Metab. 83, 902-910
   Abstract »    Full Text »
The effect of exercise training on leptin levels in obese males.
W. J. Pasman, M. S. Westerterp-Plantenga, and W. H. M. Saris (1998)
Am J Physiol Endocrinol Metab 274, E280-E286
   Abstract »    Full Text »    PDF »
The Molecular Genetics of Rodent Single Gene Obesities.
R. L. Leibel, W. K. Chung, and S. C. Chua Jr. (1997)
J. Biol. Chem. 272, 31937-31940
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Divergent Signaling Capacities of the Long and Short Isoforms of the Leptin Receptor.
C. Bjorbak, S. Uotani, B. da Silva, and J. S. Flier (1997)
J. Biol. Chem. 272, 32686-32695
   Abstract »    Full Text »    PDF »
Expression of Functional Leptin Receptors in the Human Ovary.
C. Karlsson, K. Lindell, E. Svensson, C. Bergh, P. Lind, H. Billig, L. M. S. Carlsson, and B. Carlsson (1997)
J. Clin. Endocrinol. Metab. 82, 4144-4148
   Abstract »    Full Text »    PDF »
Short Term Effects of Leptin on Hepatic Gluconeogenesis and in Vivo Insulin Action.
L. Rossetti, D. Massillon, N. Barzilai, P. Vuguin, W. Chen, M. Hawkins, J. Wu, and J. Wang (1997)
J. Biol. Chem. 272, 27758-27763
   Abstract »    Full Text »    PDF »
Leptin and Clinical Medicine: A New Piece in the Puzzle of Obesity.
G. A. Bray and D. A. York (1997)
J. Clin. Endocrinol. Metab. 82, 2771-2776
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Obesity.
M. Rosenbaum, R. L. Leibel, and J. Hirsch (1997)
N. Engl. J. Med. 337, 396-407
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The Adipose Obese Gene Product, Leptin: Evidence of a Direct Inhibitory Role in Ovarian Function.
L. J. Spicer and C. C. Francisco (1997)
Endocrinology 138, 3374-3379
   Abstract »    Full Text »    PDF »


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