Mechanisms of muscle insulin resistance in obese individuals.
Mechanisms of muscle insulin resistance in obese individuals.
复制标题
肥胖个体肌肉胰岛素抵抗的机制。
DOI：
10.1123/ijsnem.11.s1.s64
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Dohm,GL
中科院分区：
文献类型：
--
作者：
Dohm,GL
我们以前报道过肥胖个体骨骼肌的胰岛素抵抗与胰岛素信号转导和胰岛素受体酪氨酸激酶活性的降低有关。蛋白激酶C（PKC）磷酸化胰岛素受体丝氨酸/苏氨酸残基，降低酪氨酸激酶活性，导致胰岛素抵抗。用碱性磷酸酶治疗肥胖受试者的胰岛素受体恢复了酪氨酸激酶活性，表明活性降低是受体过度磷酸化的结果。用PKC抑制剂孵育人肌纤维条恢复肥胖患者肌肉中的胰岛素作用，而用佛波酯激活PKC引起瘦对照患者肌肉中的胰岛素抵抗。肥胖、胰岛素抵抗患者肌肉中PKC β亚型升高。这些数据与升高的PKC活性可能通过磷酸化胰岛素受体以降低酪氨酸激酶活性而引起胰岛素抵抗的假设一致。
We previously reported that insulin resistance in skeletal muscle of obese individuals was associated with decreases in insulin signal transduction and tyrosine kinase activity of the insulin receptor. Herein is reviewed the recently published data supporting the hypothesis that protein kinase C (PKC) phosphorylates the insulin receptor on serine/threonine residues to decrease tyrosine kinase activity and cause insulin resistance. Treatment of insulin receptors from obese subjects with alkaline phosphatase restored tyrosine kinase activity, suggesting that the reduced activity was a result of hyperphosphorylation of the receptor. Incubating human muscle fiber strips with PKC inhibitors restored insulin action in muscle of obese patients, while activating PKC with a phorbol ester caused insulin resistance in muscle from lean control patients. The beta isoform of PKC was elevated in muscle of obese, insulin-resistant patients. These data are consistent with the hypothesis that elevated PKC activity may cause insulin resistance by phosphorylating the insulin receptor to decrease tyrosine kinase activity.