Muscle-specific overexpression of CD36 reverses the insulin resistance and diabetes of MKR mice

Endocrinology
Lisa Héron-MilhavetDerek LeRoith

Abstract

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, beta-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.

References

Dec 1, 1994·The Journal of Clinical Investigation·D E Kelley, J A Simoneau
Jun 1, 1994·The Journal of Clinical Investigation·G BodenL Rossetti
Jun 30, 1998·Current Opinion in Lipidology·B H Goodpaster, D E Kelley
Sep 29, 1998·Metabolism: Clinical and Experimental·S M ChalkleyE W Kraegen
Jan 23, 1999·The Journal of Clinical Investigation·A DresnerG I Shulman
Feb 19, 1999·Metabolism: Clinical and Experimental·C A ChuA D Cherrington
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·O GavrilovaM L Reitman
May 9, 2000·The Journal of Biological Chemistry·A BonenN N Tandon
Jul 21, 2000·The Journal of Clinical Investigation·G I Shulman
Oct 24, 2000·Trends in Endocrinology and Metabolism : TEM·R N Bergman, M Ader
Nov 10, 2001·American Journal of Physiology. Endocrinology and Metabolism·F FrickJ Oscarsson
Jan 15, 2002·American Journal of Physiology. Endocrinology and Metabolism·Joost J F P LuikenArend Bonen
May 15, 2002·American Journal of Physiology. Endocrinology and Metabolism·Thongchai PratipanawatrRalph A DeFronzo
Aug 21, 2002·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·G MingroneA V Greco
Sep 17, 2002·The American Journal of Cardiology·Kitt F Petersen, Gerald I Shulman
Oct 18, 2002·The Journal of Biological Chemistry·Nianning QiTheodore W Kurtz
Jul 17, 2003·Acta Physiologica Scandinavica·B D HegartyE W Kraegen
Oct 1, 1963·The American Journal of Physiology·G M GRODSKYD F SMITH

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Citations

Jul 14, 2006·Pediatric Surgery International·Min ChenCarroll M Harmon
Mar 1, 2008·The Journal of Biological Chemistry·Zaher NahléNada A Abumrad
Oct 9, 2012·Clinical and Experimental Pharmacology & Physiology·Guang-Yao SongYong Tang
Feb 3, 2012·American Journal of Physiology. Endocrinology and Metabolism·Vladimir A LizunovSamuel W Cushman
Nov 5, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sarah J LessardJohn A Hawley
Mar 7, 2006·BMC Molecular Biology·Malin AndersenJacob Odeberg
May 19, 2011·PloS One·Ho Joong SungPaul M Hwang
Apr 26, 2012·Canadian Journal of Physiology and Pharmacology·Alpana BhattacharjeeMichael B Wheeler
Oct 13, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ande SatyanarayanaJonathan R Keller
Jun 12, 2012·Endocrinology and Metabolism Clinics of North America·David R Clemmons
Jun 12, 2012·Endocrinology and Metabolism Clinics of North America·Robert A Frost, Charles H Lang
Jan 7, 2016·Journal of Translational Medicine·G A AguirreI Castilla-Cortazar
Feb 5, 2005·The Journal of Biological Chemistry·Claire C BastieNada A Abumrad
Aug 3, 2018·Journal of Molecular Endocrinology·Louise K MetcalfeNigel Turner
Feb 27, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ping YangYaxi Chen
May 10, 2020·Animals : an Open Access Journal From MDPI·Bozena HosnedlovaHana Horna
Jul 26, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ju-Gyeong KangPaul M Hwang
Mar 7, 2014·American Journal of Physiology. Renal Physiology·Sandeep K MallipattuJohn C He

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