Shepherd P R, Navé B T, Siddle K
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, U.K.
Biochem J. 1995 Jan 1;305 ( Pt 1)(Pt 1):25-8. doi: 10.1042/bj3050025.
We have investigated the involvement of phosphoinositide (PI) 3-kinase and p70 ribosomal protein-S6 kinase (p70s6k) in mediating insulin stimulation of glycogen synthesis in 3T3-L1 adipocytes using specific inhibitors. Wortmannin inhibited PI 3-kinase activity (IC50 approximately 10 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 p70s6k, decreased insulin activation of glycogen synthase in a dose-dependent manner (IC50 approximately 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 p70s6k are involved in the signalling pathways by which insulin stimulates glycogen synthase in 3T3-L1 adipocytes.
我们使用特异性抑制剂研究了磷脂酰肌醇（PI）3激酶和p70核糖体蛋白S6激酶（p70s6k）在介导胰岛素刺激3T3-L1脂肪细胞糖原合成中的作用。渥曼青霉素抑制PI 3激酶活性（IC50约为10 nM），在100 nM时抑制作用完全。渥曼青霉素（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p70s6k激活，以剂量依赖方式降低胰岛素对糖原合酶的激活作用（IC50约为0.8 ng/ml），最大抑制率约为75%。雷帕霉素对胰岛素刺激的葡萄糖掺入糖原的抑制程度和剂量依赖性相似，而对胰岛素刺激的葡萄糖转运无影响。我们得出结论，PI 3激酶和p70s6k参与了胰岛素刺激3T3-L1脂肪细胞中糖原合酶的信号通路。
