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A more recent version of this article appeared on December 1, 2003

Papers In Press, published online ahead of print August 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300143-JLR200
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Submitted on April 7, 2003
Revised on July 29, 2003
Accepted on August 12, 2003

CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice

Jeltje R. Goudriaan, Vivian E. H. Dahlmans, Bas Teusink, D. Margriet Ouwens, Maria Febbraio, J. Anton Maassen, Johannes A. Romijn, Louis M. Havekes, and Peter J. Voshol

The Gaubius Laboratory, TNO Prevention and Health, Leiden, Leiden 2333 CK

Corresponding Author: pj.voshol{at}pg.tno.nl

Objective. CD36 (fatty acid translocase) is involved in high affinity peripheral fatty acid uptake. Mice lacking CD36 exhibit increased plasma free fatty acid and triglyceride levels and decreased glucose levels. Studies in spontaneous hypertensive rats, lacking functional CD36, link CD36 to the insulin resistance syndrome. To clarify the relationship between CD36 and insulin sensitivity in more detail, we determined insulin-mediated whole body and tissue-specific glucose uptake in CD36-deficient mice. Methods and results. Insulin-mediated whole body and tissue-specific glucose uptake was measured by D-[3H]glucose and 2-deoxy-D-[1-3H]glucose during hyperinsulinemic clamp in CD36-deficient and control mice. Whole body and muscle-specific insulin-mediated glucose uptake was significantly higher in CD36-deficient compared to control mice. In contrast, insulin completely failed to suppress hepatic glucose production in CD36 deficient mice compared to a 40% reduction in control mice. This insulin resistant state of the liver was associated with increased hepatic triglyceride content in CD36 -/- mice compared to CD36 +/+ mice (110.9 ± 12.0 and 68.9 ± 13.6 µg TG/mg protein, respectively). Moreover hepatic activation of protein kinase B by insulin, measured by Western blot, was reduced by 54%. Conclusion. Our results show a dissociation between increased muscle and decreased liver insulin sensitivity in CD36-deficient mice.


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