Hepatocyte growth factor induces glucose uptake in 3T3-L1 adipocytes through A Gab1/phosphatidylinositol 3-kinase/Glut4 pathway
Hepatocyte growth factor induces glucose uptake in 3T3-L1 adipocytes through A Gab1/phosphatidylinositol 3-kinase/Glut4 pathway
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DOI：
10.1074/jbc.m611770200
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发表时间：
2007-04-06
影响因子：
4.8
通讯作者：
Gual, Philippe
中科院分区：
文献类型：
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作者：
Bertola, Adeline;Bonnafous, Stephanie;Gual, Philippe
脂肪组织是肝细胞生长因子（HGF）的来源，循环HGF水平与人体体重指数升高有关。然而，HGF对脂肪细胞功能的影响尚未被研究。我们在这里表明，在3T3-L1脂肪细胞中，HGF刺激磷脂酰肌醇（PI） 3-激酶依赖性蛋白激酶B （PKB）活性，AS160磷酸化，Glut4易位，从而促进葡萄糖摄取。HGF和胰岛素诱导的葡萄糖摄取的初始步骤是不同的。HGF增强了Gab1的酪氨酸磷酸化，导致p85调节的PI 3激酶亚基的募集，而p85仅由IRS1在响应胰岛素时募集。在长期肿瘤坏死因子α治疗导致胰岛素抵抗的脂肪细胞中，Gab1蛋白水平强烈降低，HGF刺激的PKB激活和葡萄糖摄取也发生改变。此外，用抗糖尿病药物噻唑烷二酮治疗3T3-L1脂肪细胞，可增强HGF及其受体的表达。这些数据提供了体外HGF通过Gab1/PI 3-激酶/ PKB/ AS160途径促进葡萄糖摄取的第一个证据，该途径在肿瘤坏死因子α处理的脂肪细胞中被改变。
Adipose tissue is a source of hepatocyte growth factor ( HGF), and circulating HGF levels have been associated with elevated body mass index in human. However, the effects of HGF on adipocyte functions have not yet been investigated. We show here that in 3T3-L1 adipocytes HGF stimulates the phosphatidylinositol (PI) 3-kinase-dependent protein kinase B (PKB) activity, AS160 phosphorylation, Glut4 translocation, and consequently, glucose uptake. The initial steps involved in HGF- and insulin-induced glucose uptake are different. HGF enhanced the tyrosine phosphorylation of Gab1, leading to the recruitment of the p85-regulated subunit of PI 3-kinase, whereas p85 was exclusively recruited by IRS1 in response to insulin. In adipocytes rendered insulin-resistant by a long-lasting tumor necrosis factor alpha treatment, the protein level of Gab1 was strongly decreased, and HGF- stimulated PKB activation and glucose uptake were also altered. Moreover, treatment of 3T3-L1 adipocytes with thiazolidinedione, an anti- diabetic drug, enhanced the expression of both HGF and its receptor. These data provide the first evidence that in vitro HGF promotes glucose uptake through a Gab1/PI 3-kinase/ PKB/ AS160 pathway which was altered in tumor necrosis factor alpha-treated adipocytes.