Fuel selection in human skeletal muscle in insulin resistance - A reexamination
Fuel selection in human skeletal muscle in insulin resistance - A reexamination
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DOI：
10.2337/diabetes.49.5.677
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发表时间：
2000-05-01
期刊：
影响因子：
7.7
通讯作者：
Mandarino, LJ
中科院分区：
文献类型：
--
作者：
Kelley, DE;Mandarino, LJ
多年来，Randle葡萄糖脂肪酸循环一直被用来解释2型糖尿病或肥胖患者骨骼肌中的胰岛素抵抗。大量研究结果表明，通过提供过量脂质来人为增加脂肪氧化确实会降低全身葡萄糖氧化。然而，用啮齿动物或人类系统获得的更直接地检查肌肉燃料选择的结果已经发现，胰岛素抵抗中的骨骼肌伴随着基础条件下肌肉葡萄糖氧化的增加而不是减少，以及胰岛素刺激环境下葡萄糖氧化的减少，产生“代谢稳定性”的状态，这种情况可能有助于肌细胞内甘油三酯的积累，如在胰岛素抵抗中所观察到的，胰岛素受体信号传导的最新知识表明，肌肉中脂质产物的积累可以干扰胰岛素信号传导并产生胰岛素抵抗。因此，尽管Randle循环是有效的生理学原理，但它可能不能解释骨骼肌中的胰岛素抵抗。
For many years, the Randle glucose fatty acid cycle has been invoked to explain insulin resistance in skeletal muscle of patients with type 2 diabetes or obesity Increased fat oxidation was hypothesized to reduce glucose metabolism. The results of a number of investigations have shown that artificially increasing fat oxidation by provision of excess Lipid does decrease glucose oxidation in the whole body. However, results obtained with rodent or human systems that more directly examined muscle fuel selection have found that skeletal muscle in insulin resistance is accompanied by increased, rather than decreased, muscle glucose oxidation under basal conditions and decreased glucose oxidation under insulin-stimulated circumstances, producing a state of "metabolic inflexibility," Such a situation could contribute to the accumulation of triglyceride within the myocyte, as has been observed in insulin resistance, Recent knowledge of insulin receptor signaling indicates that the accumulation of lipid products in muscle can interfere with insulin signaling and produce insulin resistance, Therefore, although the Randle cycle is a valid physiological principle, it may not explain insulin resistance in skeletal muscle.