This Article Full Text Full Text (PDF) All Versions of this Article: 145/10/4667    most recent Author Manuscript (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 Héron-Milhavet, L. Articles by LeRoith, D. Search for Related Content PubMed PubMed Citation Articles by Héron-Milhavet, L. Articles by LeRoith, D.

Muscle-Specific Overexpression of CD36 Reverses the Insulin Resistance and Diabetes of MKR Mice

Diabetes Branch (L.H.-M., M.H., S.Y., O.G., S.P., W.C.J., H.K., D.H., D.L.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Mouse Metabolic Core Facility (O.G., S.P., W.C.J.), Université Sidi Mohammed Ben Abdellah (A.I.), Centre d’Etudes Universitaires de Taza, Taza 1223, Morocco; Endocrine and Diabetes Research Group (D.Y., Z.A., J.J., M.B.W.), Department of Physiology, University of Toronto, Toronto, Canada M5S 1AB; and Department of Physiology and Biophysics (N.A.A.), State University of New York, Stony Brook, New York 11794

Address all correspondence and requests for reprints to: Derek LeRoith, M.D., Ph.D., Diabetes Branch, NIDDK, Room 8D12, Building 10, National Institutes of Health, Bethesda, Maryland 20892-1758. E-mail: Derek{at}helix.nih.gov.

Insulin resistance is one of the primary characteristics of type 2 diabetes. Mice overexpressing a dominant-negative IGF-I receptor specifically in muscle (MKR mice) demonstrate severe insulin resistance with high levels of serum and tissue lipids and eventually develop type 2 diabetes at 5–6 wk of age. To determine whether lipotoxicity plays a role in the progression of the disease, we crossed MKR mice with mice overexpressing a fatty acid translocase, CD36, in skeletal muscle. The double-transgenic MKR/CD36 mice showed normalization of the hyperglycemia and the hyperinsulinemia as well as a marked improvement in liver insulin sensitivity. The MKR/CD36 mice also exhibited normal rates of fatty acid oxidation in skeletal muscle when compared with the decreased rate of fatty acid oxidation in MKR. With the reduction in insulin resistance, ß-cell function returned to normal. These and other results suggest that the insulin resistance in the MKR mice is associated with increased muscle triglycerides levels and that whole-body insulin resistance can be, at least partially, reversed in association with a reduction in muscle triglycerides levels, although the mechanisms are yet to be determined.

This article has been cited by other articles:

				Z. Nahle, M. Hsieh, T. Pietka, C. T. Coburn, P. A. Grimaldi, M. Q. Zhang, D. Das, and N. A. Abumrad CD36-dependent Regulation of Muscle FoxO1 and PDK4 in the PPAR{delta}/{beta}-mediated Adaptation to Metabolic Stress J. Biol. Chem., May 23, 2008; 283(21): 14317 - 14326. [Abstract] [Full Text] [PDF]

				T. Obermeyer, P. Fraisl, C. C. DiRusso, and P. N. Black Topology of the yeast fatty acid transport protein Fat1p: mechanistic implications for functional domains on the cytosolic surface of the plasma membrane J. Lipid Res., November 1, 2007; 48(11): 2354 - 2364. [Abstract] [Full Text] [PDF]

				J. E. Ayala, D. P. Bracy, O. P. McGuinness, and D. H. Wasserman Considerations in the Design of Hyperinsulinemic-Euglycemic Clamps in the Conscious Mouse Diabetes, February 1, 2006; 55(2): 390 - 397. [Abstract] [Full Text] [PDF]

				Y. Toyoshima, O. Gavrilova, S. Yakar, W. Jou, S. Pack, Z. Asghar, M. B. Wheeler, and D. LeRoith Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes Endocrinology, September 1, 2005; 146(9): 4024 - 4035. [Abstract] [Full Text] [PDF]

				C. C. Bastie, Z. Nahle, T. McLoughlin, K. Esser, W. Zhang, T. Unterman, and N. A. Abumrad FoxO1 Stimulates Fatty Acid Uptake and Oxidation in Muscle Cells through CD36-dependent and -independent Mechanisms J. Biol. Chem., April 8, 2005; 280(14): 14222 - 14229. [Abstract] [Full Text] [PDF]

				M. A. Maxwell, M. E. Cleasby, A. Harding, A. Stark, G. J. Cooney, and G. E. O. Muscat Nur77 Regulates Lipolysis in Skeletal Muscle Cells: EVIDENCE FOR CROSS-TALK BETWEEN THE {beta}-ADRENERGIC AND AN ORPHAN NUCLEAR HORMONE RECEPTOR PATHWAY J. Biol. Chem., April 1, 2005; 280(13): 12573 - 12584. [Abstract] [Full Text] [PDF]