Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance

被引:121
作者
Wredenberg, Anna
Freyer, Christoph
Sandstrom, Marie E.
Katz, Abram
Wibom, Rolf
Westerblad, Hakan
Larsson, Nils-Goran [1 ]
机构
[1] Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Stockholm, Sweden
[2] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden
关键词
mitochondria; mtDNA; insulin resistance; diabetes; respiratory chain; oxidative phosphorylation;
D O I
10.1016/j.bbrc.2006.09.029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Insulin resistance in skeletal muscle is a characteristic feature of diabetes mellitus type 2 (DM2). Several lines of circumstantial evidence suggest that reduced mitochondrial oxidative phosphorylation capacity in skeletal muscle is a primary defect causing insulin resistance and subsequent development of DM2. We have now experimentally tested this hypothesis by characterizing glucose homeostasis in tissue-specific knockout mice with progressive respiratory chain dysfunction selectively in skeletal muscle. Surprisingly, these knockout mice are not diabetic and have an increased peripheral glucose disposal when subjected to a glucose tolerance test. Studies of isolated skeletal muscle from knockout animals show an increased basal glucose uptake and a normal increase of glucose uptake in response to insulin. In summary, our findings indicate that mitochondrial dysfunction in skeletal muscle is not a primary etiological event in DM2. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:202 / 207
页数:6
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