CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice
| Autor: | 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. |
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| Přispěvatelé: | Gaubius Instituut TNO |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Blood Glucose
Hepatic steatosis Biomedical Research muscle Fatty acid transport Antigens CD36 fatty acid blood level Western blotting Eating Mice CD36 antigen Insulin glucose Glucose metabolism hemic and immune systems Hyperinsulinemic clamp Lipids unclassified drug Liver hyperinsulinemia enzyme deficiency wild type triacylglycerol circulatory and respiratory physiology Signal Transduction spontaneously hypertensive rat animal experiment Tritium animal tissue male parasitic diseases insulin sensitivity Animals controlled study Muscle Skeletal Biology mouse Triglycerides nonhuman animal model Body Weight glucose transport enzyme activation triacylglycerol blood level Rats Mice Inbred C57BL glucose blood level protein kinase B fatty acid Insulin Resistance Gene Deletion |
| Zdroj: | Journal of Lipid Research, 12, 44, 2270-2277 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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