Increased adipose tissue expression of Grb14 in several models of insulin resistance
Increased adipose tissue expression of Grb14 in several models of insulin resistance
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DOI：
10.1096/fj.03-0824fje
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发表时间：
2004-04-01
期刊：
影响因子：
4.8
通讯作者：
Burnol, AF
中科院分区：
文献类型：
--
作者：
Cariou, B;Capitaine, N;Burnol, AF
Grb 14是胰岛素信号的效应子，在体外直接抑制胰岛素受体催化活性。在这里，我们研究了Grb 14及其结合伴侣ZIP（PKC zeta相互作用蛋白）的表达是否在2型糖尿病啮齿动物和人类的胰岛素抵抗过程中受到调节。Grb 14在ob/ob小鼠和Goto-Kakizaki（GK）大鼠的脂肪组织中表达增加，而在肝脏中没有差异。与对照组相比，2型糖尿病受试者的皮下脂肪组织也有所增加。ZIP表达在ob/ob小鼠和2型糖尿病患者的脂肪组织中增加，但在GK大鼠中没有变化。然后在3 T3-F442 A脂肪细胞中研究Grb 14和ZIP表达的激素调节。在该模型中，胰岛素刺激Grb 14表达，而TNF-α增加ZIP表达。此外，胰岛素增敏药物噻唑烷二酮类（TZDs）降低3 T3-F442 A脂肪细胞中Grb 14的表达。最后，我们研究了Grb 14在ob/ob小鼠中表达的动态调节，在几种条件下改善其胰岛素敏感性。长期禁食和二甲双胍治疗显著降低了子宫周围脂肪组织中Grb 14的表达，而TZD治疗后仅呈减少趋势。综上所述，这些结果表明，脂肪组织中Grb 14表达的调节可能在胰岛素敏感性中发挥生理作用。
Grb14 is an effector of insulin signaling, which directly inhibits insulin receptor catalytic activity in vitro. Here, we investigated whether the expression of Grb14 and its binding partner ZIP (PKC zeta interacting protein) is regulated during insulin resistance in type 2 diabetic rodents and humans. Grb14 expression was increased in adipose tissue of both ob/ob mice and Goto-Kakizaki ( GK) rats, whereas there was no difference in liver. An increase was also observed in subcutaneous adipose tissue of type 2 diabetic subjects when compared with controls. ZIP expression was increased in adipose tissue of ob/ob mice and type 2 diabetic patients, but it did not vary in GK rats. Hormonal regulation of Grb14 and ZIP expression was then investigated in 3T3-F442A adipocytes. In this model, insulin stimulated Grb14 expression, while TNF-alpha increased ZIP expression. Moreover, the insulin-sensitizing drugs thiazolidinediones (TZDs) decreased Grb14 expression in 3T3-F442A adipocytes. Finally, we investigated the dynamic regulation of Grb14 expression in ob/ob mice in several conditions improving their insulin sensitivity. Prolonged fasting and treatment with metformin significantly decreased Grb14 expression in peri-epidydimal adipose tissue, while there was only a trend to a diminution after TZD treatment. Taken together, these results suggest that the regulation of Grb14 expression in adipose tissue may play a physiological role in insulin sensitivity.