Brüning J C, Michael M D, Winnay J N, Hayashi T, Hörsch D, Accili D, Goodyear L J, Kahn C R
Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Mol Cell. 1998 Nov;2(5):559-69. doi: 10.1016/s1097-2765(00)80155-0.
Skeletal muscle insulin resistance is among the earliest detectable defects in humans with type 2 diabetes mellitus. To determine the contribution of muscle insulin resistance to the metabolic phenotype of diabetes, we used the Cre-loxP system to disrupt the insulin receptor gene in mouse skeletal muscle. The muscle-specific insulin receptor knockout mice exhibit a muscle-specific > 95% reduction in receptor content and early signaling events. These mice display elevated fat mass, serum triglycerides, and free fatty acids, but blood glucose, serum insulin, and glucose tolerance are normal. Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than previously recognized.
骨骼肌胰岛素抵抗是2型糖尿病患者最早可检测到的缺陷之一。为了确定肌肉胰岛素抵抗对糖尿病代谢表型的影响，我们使用Cre-loxP系统破坏小鼠骨骼肌中的胰岛素受体基因。肌肉特异性胰岛素受体敲除小鼠的受体含量和早期信号事件显示肌肉特异性降低>95%。这些小鼠的脂肪量、血清甘油三酯和游离脂肪酸升高，但血糖、血清胰岛素和糖耐量正常。因此，肌肉中的胰岛素抵抗导致了与2型糖尿病相关的脂肪代谢改变，但肌肉以外的组织似乎比之前认为的更多地参与胰岛素调节的葡萄糖代谢。
