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-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 microg 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.
Goudriaan
Jeltje R
JR
TNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands.
Dahlmans
Vivian E H
VE
Teusink
Bas
B
Ouwens
D Margriet
DM
Febbraio
Maria
M
Maassen
J Anton
JA
Romijn
Johannes A
JA
Havekes
Louis M
LM
Voshol
Peter J
PJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism*; D004435:Eating; D017353:Gene Deletion; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism; D014316:Tritium
D001786:Blood Glucose; D018955:CD36 Antigens; D007328:Insulin; D008055:Lipids; D014280:Triglycerides; D014316:Tritium