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1Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; 2Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; 3Thrombosis Research Laboratory, Otsuka Maryland Medicinal Laboratories, Rockville, Maryland; 4Section of Endocrinology and Metabolism, Wake Forest University School of Medicine and Baptist Medical Center, Winston-Salem, North Carolina; and 5Department of Molecular Genetics, Maastricht University, Maastricht, The Netherlands
Submitted 27 March 2006 ; accepted in final form 12 April 2006
An increased rate of fatty acid transport into skeletal muscle has been has been linked to the accumulation of intramuscular lipids and insulin resistance, and red muscles are more susceptible than white muscles in developing fatty acid-mediated insulin resistance. Therefore, we examined in Zucker diabetic fatty (ZDF) rats, relative to lean rats, 1) whether rates of fatty acid transport and transporters (FAT/CD36 and FABPpm) were upregulated in skeletal muscle during the transition from insulin resistance (week 6) to type 2 diabetes (weeks 12 and 24), 2) whether such changes occurred primarily in red skeletal muscle, and 3) whether changes in FAT/CD36 and GLUT4 were correlated. In red muscles of ZDF compared with lean rats, the rates of fatty acid transport were upregulated (+66%) early in life (week 6). Compared with the increase in fatty acid transport in lean red muscle from weeks 12–24 (+57%), the increase in fatty acid transport rate in ZDF red muscle was 50% greater during this same period. In contrast, no differences in fatty acid transport rates were observed in the white muscles of lean and ZDF rats at any time (weeks 6–24). In red muscle only, there was an inverse relationship between FAT/CD36 and GLUT4 protein expression as well as their plasmalemmal content. These studies have shown that, 1) before the onset of diabetes, as well as during diabetes, fatty acid transport and FAT/CD36 expression and plasmalemmal content are upregulated in ZDF rats, but importantly, 2) these changes occurred only in red, not white, muscles of ZDF rats.
insulin resistance; diabetes; plasma membrane-associated fatty acid-binding protein; fatty acid translocase messenger ribonucleic acid; plasma membrane fatty acid-binding protein messenger ribonucleic acid; glucose transporter 4; Zucker diabetic fatty rat
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