Johnson Sam A, Denton Richard M
Department of Biochemistry, University of Bristol, University Walk, Clifton, Bristol BS8 1TD, U.K.
Biochem J. 2003 Jan 15;369(Pt 2):351-6. doi: 10.1042/BJ20020920.
In isolated rat adipocytes, the insulin stimulation of pyruvate dehydrogenase can be partially inhibited by inhibitors of PI3K (phosphoinositide 3-kinase) and MEK1/2 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase). In combination, U0126 and wortmannin completely block the insulin stimulation of pyruvate dehydrogenase. It is concluded that the effect of insulin on pyruvate dehydrogenase in rat adipocytes involves two distinct signalling pathways: one is sensitive to wortmannin and the other to U0126. The synthetic phosphoinositolglycan PIG41 can activate pyruvate dehydrogenase but the activation is only approx. 30% of the maximal effect of insulin. This modest activation can be completely blocked by wortmannin alone, suggesting that PIG41 acts through only one of the pathways leading to the activation of pyruvate dehydrogenase.
在分离的大鼠脂肪细胞中,胰岛素对丙酮酸脱氢酶的刺激作用可被磷脂酰肌醇-3激酶(PI3K)抑制剂和丝裂原活化蛋白激酶/细胞外信号调节激酶激酶1/2(MEK1/2)抑制剂部分抑制。U0126和渥曼青霉素联合使用可完全阻断胰岛素对丙酮酸脱氢酶的刺激作用。得出的结论是,胰岛素对大鼠脂肪细胞中丙酮酸脱氢酶的作用涉及两条不同的信号通路:一条对渥曼青霉素敏感,另一条对U0126敏感。合成的磷酸肌醇聚糖PIG41可激活丙酮酸脱氢酶,但其激活作用仅约为胰岛素最大作用的30%。这种适度的激活作用可被单独的渥曼青霉素完全阻断,这表明PIG41仅通过导致丙酮酸脱氢酶激活的其中一条信号通路发挥作用。