Protein kinase C modulates insulin action in human skeletal muscle
Protein kinase C modulates insulin action in human skeletal muscle
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DOI：
10.1152/ajpendo.2000.278.3.e553
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发表时间：
2000-03-01
影响因子：
5.1
通讯作者：
Dohm, GL
中科院分区：
文献类型：
--
作者：
Cortright, RN;Azevedo, JL;Dohm, GL
来自细胞系和啮齿动物的充分证据表明，蛋白激酶C（PKC）过表达/活性升高导致胰岛素抵抗。因此，本研究确定了PKC激活/抑制对胰岛素介导的葡萄糖转运在孵育的人骨骼肌和原代脂肪细胞的影响，以辨别PKC在胰岛素作用中的潜在作用。将来自肥胖、胰岛素抵抗和胰岛素敏感患者的腹直肌肌条或脂肪细胞在基础和胰岛素（100 nM）刺激条件下，在存在GF 109203 X（GF）（一种PKC抑制剂）或12-脱氧佛波醇13-苯乙酸酯20-乙酸酯（dPPA）（一种PKC激活剂）的情况下进行体外孵育。PKC抑制对基础葡萄糖转运无影响。GF使胰岛素刺激的2-脱氧葡萄糖（2-DOG）转运增加（P < 0.05），约为基础水平的2倍。GF加胰岛素也使胰岛素受体酪氨酸磷酸化增加48%（P < 0.05），磷脂酰肌醇3-激酶（PI 3-kinase）活性增加50%（P < 0.05）。在人原代脂肪细胞中观察到GF对葡萄糖摄取的类似结果。PKC活性升高与胰岛素抵抗相关的假说的进一步支持来自以下发现：通过dPPA激活PKC与胰岛素刺激的2-DOG转运减少40%（P < 0.05）相关，胰岛素敏感性肌肉与GF孵育也导致胰岛素作用增强（类似于高于基础的3倍）。这些数据表明，某些PKC抑制剂增加胰岛素介导的葡萄糖摄取，并表明PKC可能调节胰岛素在人骨骼肌中的作用。
There is good evidence from cell lines and rodents that elevated protein kinase C (PKC) overexpression/activity causes insulin resistance. Therefore, the present study determined the effects of PKC activation/inhibition on insulin-mediated glucose transport in incubated human skeletal muscle and primary adipocytes to discern a potential role for PKC in insulin action. Rectus abdominus muscle strips or adipocytes from obese, insulin-resistant, and insulin-sensitive patients were incubated in vitro under basal and insulin (100 nM)-stimulated conditions in the presence of GF 109203X (GF), a PKC inhibitor, or 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), a PKC activator. PKC inhibition had no effect on basal glucose transport. GF increased (P < 0.05) insulin-stimulated 2-deoxyglucose (2-DOG) transport approximately twofold above basal. GF plus insulin also increased (P < 0.05) insulin receptor tyrosine phosphorylation 48% and phosphatidylinositol 3-kinase (PI 3-kinase) activity similar to 50% (P < 0.05) vs. insulin treatment alone. Similar results for GF on glucose uptake were observed in human primary adipocytes. Further support for the hypothesis that elevated PKC activity is related to insulin resistance comes from the finding that PKC activation by dPPA was associated with a 40% decrease (P < 0.05) in insulin-stimulated 2-DOG transport, incubation of insulin-sensitive muscles with GF also resulted in enhanced insulin action (similar to 3-fold above basal). These data demonstrate that certain PKC inhibitors augment insulin-mediated glucose uptake and suggest that PKC may modulate insulin action in human skeletal muscle.