Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle
Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle
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DOI：
10.1172/jci8305
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发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
Shulman, GI
中科院分区：
文献类型：
--
作者：
Kim, JK;Michael, MD;Shulman, GI
肥胖和骨骼肌胰岛素抵抗是2型糖尿病发病的两个主要因素。具有肌肉特异性胰岛素受体基因失活（MIRKO）的小鼠血糖正常，但脂肪量增加。为了确定这种重要关联的潜在机制，我们检查了MIRKO特定组织中的胰岛素作用，并在高胰岛素-血糖条件下控制小鼠。我们发现胰岛素刺激的肌肉葡萄糖转运和糖原合成在MIRKO小鼠中减少了约80%，而胰岛素刺激的脂肪葡萄糖转运在MIRKO小鼠中增加了三倍。这些数据表明，肌肉中的选择性胰岛素抵抗促进底物重新分配到脂肪组织，从而导致肥胖增加和糖尿病前期综合征的发展。
Obesity and insulin resistance in skeletal muscle are two major factors in the pathogenesis of type 2 diabetes. Mice with muscle-specific inactivation of the insulin receptor gene (MIRKO) are normo-glycemic but have increased fat mass. To identify the potential mechanism for this important association, we examined insulin action in specific tissues of MIRKO and control mice under hyperinsulinemic-euglycemic conditions. We found that insulin-stimulated muscle glucose transport and glycogen synthesis were decreased by about 80% in MIRKO mice, whereas insulin-stimulated fat glucose transport was increased threefold in MIRKO mice. These data demonstrate that selective insulin resistance in muscle promotes redistribution of substrates to adipose tissue thereby contributing to increased adiposity and development of the prediabetic syndrome.