Leptin stimulates glucose transport and glycogen synthesis in C2C12 myotubes: Evidence for a PI3-kinase mediated effect
Leptin stimulates glucose transport and glycogen synthesis in C2C12 myotubes: Evidence for a PI3-kinase mediated effect
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DOI：
10.1007/s001250050722
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发表时间：
1997-05-01
期刊：
影响因子：
8.2
通讯作者：
Haring, HU
中科院分区：
文献类型：
--
作者：
Berti, L;Kellerer, M;Haring, HU
最近的研究表明，瘦素损害胰岛素信号传导，即大鼠-1成纤维细胞、NIH 3 T3细胞和HepG 2细胞中的胰岛素受体自磷酸化和胰岛素受体底物（IRS）-1磷酸化。为了评估瘦素是否可能损害胰岛素在肌肉组织中的作用，我们研究了胰岛素和瘦素在肌细胞系统即C2 C12肌管中的相互作用。C2 C12细胞与瘦素（1-500 ng/ml）预孵育不显著影响胰岛素刺激的葡萄糖转运和糖原合成（1.8至2倍刺激）;然而，瘦素本身（1 ng/ml）能够模拟约80-90%的胰岛素对葡萄糖转运和糖原合成的作用。磷脂酰肌醇-3（PI 3）-激酶抑制剂渥曼青霉素和蛋白激酶C抑制剂H7均抑制葡萄糖转运和糖原合成，而SG-激酶抑制剂雷帕霉素则无影响。我们确定瘦素的作用是否通过IRS-1和PI 3-激酶的激活而发生。瘦素不刺激IRS-1免疫沉淀物中的PI 3-激酶活性;然而，PI 3-激酶活化可在p85 α免疫沉淀物中得到证实（基础值的3.04 +/- 1.5倍）。总之，数据提供了胰岛素受体和瘦素受体的信号链之间的正串扰的第一个证据。C2 C12肌管中的瘦素模拟物胰岛素对葡萄糖转运和糖原合成的影响最可能通过PI 3-激酶的活化。Leptin的这种作用独立于C2 C12细胞中IRS-1的激活而发生。
It was recently shown that leptin impairs insulin signalling, i.e. insulin receptor autophosphorylation and insulin-receptor substrate (IRS)-1 phosphorylation in rat-1 fibroblasts, NIH3T3 cells and HepG2 cells. To evaluate whether leptin might impair the effects of insulin in muscle tissue we studied the interaction of insulin and leptin in a muscle cell system, i.e. C2C12 myotubes. Preincubation of C2C12 cells with leptin (1-500 ng/ml) did not significantly affect insulin stimulated glucose transport and glycogen synthesis (1.8 to 2 fold stimulation); however, leptin by itself (1 ng/ml) was able to mimic approximately 80-90% of the insulin effect on glucose transport and glycogen synthesis. Both glucose transport as well as glycogen synthesis were inhibited by the phosphatidylinositol-3 (PI3)-kinase inhibitor wortmannin and the protein kinase C inhibitor H7 while no effect was observed with the SG-kinase inhibitor rapamycin. We determined whether the effect of leptin occurs through activation of IRS-1 and PI3-kinase. Leptin did not stimulate PI3-kinase activity in IRS-1 immunoprecipitates; however, PI3-kinase activation could be demonstrated in p85 alpha immunoprecipitates (3.04 +/- 1.5 fold of basal). In summary the data provide the first evidence for a positive crosstalk between the signalling chain of the insulin receptor and the leptin receptor. Leptin mimics in C2C12 myotubes insulin effects on glucose transport and glycogen synthesis most likely through activation of PI3-kinase. This effect of leptin occurs independently of IRS-1 activation in C2C12 cells.