首页> 外文期刊>The Biochemical Journal >INSULIN STIMULATION OF GLYCOGEN SYNTHESIS AND GLYCOGEN SYNTHASE ACTIVITY IS BLOCKED BY WORTMANNIN AND RAPAMYCIN IN 3T3-L1 ADIPOCYTES - EVIDENCE FOR THE INVOLVEMENT OF PHOSPHOINOSITIDE 3-KINASE AND P70 RIBOSOMAL PROTEIN-S6 KINASE
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INSULIN STIMULATION OF GLYCOGEN SYNTHESIS AND GLYCOGEN SYNTHASE ACTIVITY IS BLOCKED BY WORTMANNIN AND RAPAMYCIN IN 3T3-L1 ADIPOCYTES - EVIDENCE FOR THE INVOLVEMENT OF PHOSPHOINOSITIDE 3-KINASE AND P70 RIBOSOMAL PROTEIN-S6 KINASE

机译:胰岛素刺激3T3-L1磷酸化中的渥曼青霉素和雷帕霉素阻碍了糖原合成和糖原合成酶的活性-磷酸肌醇3-激酶和P70核糖体蛋白-S6激酶参与的证据

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摘要

We have investigated the involvement of phosphoinositide (PI) 3-kinase and p70 ribosomal protein-S6 kinase (p70(s6k)) in mediating insulin stimulation of glycogen synthesis in 3T3-L1 adipocytes using specific inhibitors. Wortmannin inhibited PI 3-kinase activity (IC50 approximate to 16 nM), inhibition being complete at 100 nm. Wortmannin (100 nM) completely blocked the ability of insulin to activate glycogen synthase in 3T3-L1 adipocytes and the ability of insulin to stimulate glucose incorporation into glycogen in 3T3-L1 fibroblasts. Rapamycin, which blocks insulin-stimulated activation of p70(s6k), decreased insulin activation of glycogen synthase in a dose-dependent manner (IC50 similar to 0.8 ng/ml), with a maximum approx. 75% inhibition of insulin's stimulatory effect. Rapamycin inhibited insulin-stimulated glucose incorporation into glycogen to a similar extent and with similar dose-dependency, while having no effect on insulin-stimulated glucose transport. We conclude that PI 3-kinase and p70(s6k) are involved in the signalling pathways by which insulin stimulates glycogen synthase in 3T3-L1 adipocytes.
机译:我们已经研究了磷酸肌醇(PI)3-激酶和p70核糖体蛋白-S6激酶(p70(s6k))在使用特定抑制剂介导胰岛素刺激3T3-L1脂肪细胞糖原合成中的作用。 Wortmannin抑制PI 3-激酶活性(IC50约16 nM),抑制作用在100 nm处完成。 Wortmannin(100 nM)完全阻断了胰岛素激活3T3-L1脂肪细胞中糖原合酶的能力以及胰岛素刺激3T3-L1成纤维细胞中葡萄糖掺入糖原的能力。雷帕霉素可阻断胰岛素刺激的p70(s6k)激活,它以剂量依赖的方式(IC50类似于0.8 ng / ml)降低糖原合酶的胰岛素激活,最大约为。抑制75%的胰岛素刺激作用。雷帕霉素以类似的程度和相似的剂量依赖性抑制胰岛素刺激的葡萄糖掺入糖原中,而对胰岛素刺激的葡萄糖转运没有影响。我们得出结论,PI 3-激酶和p70(s6k)参与了胰岛素刺激3T3-L1脂肪细胞中糖原合酶的信号传导途径。

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