CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice
CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice
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DOI：
10.1194/jlr.m300143-jlr200
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发表时间：
2003-12-01
影响因子：
6.5
通讯作者：
Voshol, PJ
中科院分区：
文献类型：
--
作者：
Goudriaan, JR;Dahlmans, VEH;Voshol, PJ
CD 36（脂肪酸转位酶）参与高亲和力外周脂肪酸摄取。缺乏CD 36的小鼠表现出增加的血浆游离脂肪酸和甘油三酯（TG）水平和降低的葡萄糖水平。在缺乏功能性CD 36的自发性高血压大鼠中的研究将CD 36与胰岛素抵抗综合征联系起来。为了更详细地阐明CD 36与胰岛素敏感性之间的关系，我们测定了CD 36缺陷（CD 36（-/-））小鼠中胰岛素介导的全身和组织特异性葡萄糖摄入。在CD 36（-/-）和野生型对照同窝小鼠（CD 36（+/+））的高胰岛素钳夹期间，通过D-[H-3]葡萄糖和2-脱氧-D-[1-H-3]葡萄糖测量胰岛素介导的全身和组织特异性葡萄糖摄取。CD 36（-/-）小鼠的全身和肌肉特异性胰岛素介导的葡萄糖摄取显著高于CD 36（+/+）小鼠。相比之下，胰岛素完全不能抑制CD 36（-/-）小鼠的内源性葡萄糖生成，而CD 36（+/+）小鼠的内源性葡萄糖生成减少了40%。与CD 36（+/+）小鼠相比，这种肝脏胰岛素抵抗状态与CD 36（-/-）小鼠肝脏TG含量增加相关（分别为110.9 +/- 12.0和68.9 +/- 13.6 mug TG/mg蛋白）。此外，蛋白质印迹法测定的胰岛素对蛋白激酶B的肝脏激活降低了54%。我们的研究结果表明，在CD 36（-/-）小鼠中，肌肉增加和肝脏胰岛素敏感性降低之间存在分离。-Goudriaan，J.R.，V. E. H. Dahlmans，B. Teusink，D. M.欧文斯湾Febbraio，J. A. Maassen，J. A.罗明湖A Havekes和PJ Voshol CD 36缺乏会增加小鼠肌肉的胰岛素敏感性，但会诱导肝脏的胰岛素抵抗。
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-[H-3]glucose and 2-deoxy-D-[1-H-3] 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 mug 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, J.R., V. E. H. Dahlmans, B. Teusink, D. M. Ouwens, M. Febbraio, J. A. Maassen, J. A. Romijn, L. A Havekes, and P. J. Voshol. CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice.