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

CD36 (fatty acid translocase) is involved in high-affinity peripheral fatty acid uptake. Mice lacking CD36 exhibit increased plasma free fatty acid and triglyceride (TG) levels and decreased glucose levels. Studies in spontaneous hypertensive rats lacking functional CD36 link CD36 to the insulin-res...

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Bibliographic Details
Published in:	Journal of lipid research Vol. 44; no. 12; pp. 2270 - 2277
Main Authors:	Goudriaan, Jeltje R., Dahlmans, Vivian E.H., Teusink, Bas, Ouwens, D. Margriet, Febbraio, Maria, Maassen, J. Anton, Romijn, Johannes A., Havekes, Louis M., Voshol, Peter J.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-12-2003 Elsevier
Subjects:	Animals Blood Glucose - analysis Body Weight CD36 Antigens - genetics CD36 Antigens - metabolism Eating fatty acid transport Gene Deletion glucose metabolism hepatic steatosis hyperinsulinemic clamp Insulin - metabolism Insulin - pharmacology Insulin Resistance - physiology Lipids - blood Liver - drug effects Liver - metabolism Mice Mice, Inbred C57BL Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Rats Signal Transduction - drug effects Triglycerides - metabolism Tritium hyperinsulinemic clamp fatty acid transport glucose metabolism hepatic steatosis
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Summary:	CD36 (fatty acid translocase) is involved in high-affinity peripheral fatty acid uptake. Mice lacking CD36 exhibit increased plasma free fatty acid and triglyceride (TG) 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 (CD36−/−) mice. 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−/− and wild-type control littermates (CD36+/+) mice. Whole-body and muscle-specific insulin-mediated glucose uptake was significantly higher in CD36−/− compared with CD36+/+ mice. In contrast, insulin completely failed to suppress endogenous glucose production in CD36−/− mice compared with a 40% reduction in CD36+/+ mice. This insulin-resistant state of the liver was associated with increased hepatic TG content in CD36−/− mice compared with 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%. Our results show a dissociation between increased muscle and decreased liver insulin sensitivity in CD36−/− mice.
ISSN:	0022-2275 1539-7262
DOI:	10.1194/jlr.M300143-JLR200