Usui I, Haruta T, Takata Y, Iwata M, Uno T, Takano A, Ueno E, Ishibashi O, Ishihara H, Wada T, Sasaoka T, Kobayashi M
First Department of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Horm Metab Res. 1999 Oct;31(10):546-52. doi: 10.1055/s-2007-978793.
Non-esterified fatty acids are thought to be one of the causes for insulin resistance. However, the molecular mechanism of fatty acid-induced insulin resistance is not clearly known. In this study, we first examined the effect of palmitate on insulin signaling in 3T3-L1 adipocytes. We found that 1h treatment with 1 mmol/l palmitate had no effect on insulin binding, tyrosine phosphorylation of insulin receptors, 185 kDa proteins and Shc, and PI3 kinase activity in 3T3-L1 adipocytes. Then, the effects of palmitate on MAP kinase activity and glucose uptake in fully differentiated 3T3-L1 adipocytes were compared with those in poorly differentiated 3T3-L1 cells and in HIRc-B cells. Palmitate treatment had no effect on MAP kinase activity in fully differentiated 3T3-L1 adipocytes, while it inhibited MAP kinase in poorly differentiated 3T3-L1 cells and HIRc-B cells. Glucose transport in 3T3-L1 adipocytes treated with palmitate for 1 h, 4 h and 16 h was higher than that in control cells, but palmitate treatment caused a rightward shift of the insulin-dose responsive curve for glucose uptake in HIRc-B cells. Palmitate treatment did not significantly affect basal and insulin-stimulated GLUT4 translocation. When the cells were treated with PD98059, a specific MEK inhibitor, insulin-stimulated glucose uptake was not affected in 3T3-L1 adipocytes, while it was almost completely inhibited in HIRc-B cells. These results suggest the primary effect of palmitate on adipocytes may not involve insulin resistance of adipocytes themselves.
非酯化脂肪酸被认为是胰岛素抵抗的原因之一。然而，脂肪酸诱导胰岛素抵抗的分子机制尚不清楚。在本研究中，我们首先检测了棕榈酸对3T3-L1脂肪细胞胰岛素信号传导的影响。我们发现，用1 mmol/l棕榈酸处理1小时对3T3-L1脂肪细胞中的胰岛素结合、胰岛素受体的酪氨酸磷酸化、185 kDa蛋白和Shc以及PI3激酶活性没有影响。然后，将棕榈酸对完全分化的3T3-L1脂肪细胞中MAP激酶活性和葡萄糖摄取的影响与未充分分化的3T3-L1细胞和HIRc-B细胞中的影响进行了比较。棕榈酸处理对完全分化的3T3-L1脂肪细胞中的MAP激酶活性没有影响，而它抑制了未充分分化的3T3-L1细胞和HIRc-B细胞中的MAP激酶。用棕榈酸处理1小时、4小时和16小时的3T3-L1脂肪细胞中的葡萄糖转运高于对照细胞，但棕榈酸处理导致HIRc-B细胞中葡萄糖摄取的胰岛素剂量反应曲线向右移动。棕榈酸处理对基础和胰岛素刺激的GLUT4转位没有显著影响。当用特异性MEK抑制剂PD98059处理细胞时，胰岛素刺激的葡萄糖摄取在3T3-L1脂肪细胞中不受影响，而在HIRc-B细胞中几乎被完全抑制。这些结果表明，棕榈酸对脂肪细胞的主要作用可能不涉及脂肪细胞自身的胰岛素抵抗。
