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

Author: Goudriaan, J.R. · Dahlmans, V.E.H. · Teusink, B. · Ouwens, D.M. · Febbraio, M. · Maassen, J.A. · Romijn, J.A. · Havekes, L.M. · Voshol, P.J.
Type:article
Date:2003
Institution: Gaubius Instituut TNO
Source:Journal of Lipid Research, 12, 44, 2270-2277
Identifier: 237489
doi: doi:10.1194/jlr.M300143-JLR200
Keywords: Biology · Biomedical Research · Fatty acid transport · Glucose metabolism · Hepatic steatosis · Hyperinsulinemic clamp · CD36 antigen · fatty acid · glucose · protein kinase B · triacylglycerol · unclassified drug · animal experiment · animal model · animal tissue · controlled study · enzyme activation · enzyme deficiency · fatty acid blood level · glucose blood level · glucose transport · hyperinsulinemia · insulin sensitivity · male · mouse · muscle · nonhuman · spontaneously hypertensive rat · triacylglycerol blood level · Western blotting · wild type · Animals · Antigens, CD36 · Blood Glucose · Body Weight · Eating · Gene Deletion · Insulin · Insulin Resistance · Lipids · Liver · Mice · Mice, Inbred C57BL · Muscle, Skeletal · Rats · Signal Transduction · Triglycerides · Tritium

Abstract

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.