脂肪细胞在肝细胞胰岛素耐受过程中的作用

The Effects of Fat Cells on the Development of Hepatic Insulin Resistance

目的研究脂肪细胞在不同分化阶段对肝细胞胰岛素抵抗的影响。方法体外诱导3T3-L1脂肪前体细胞分化,细胞内脂滴增加,逐步分化成脂肪细胞。采用不同分化阶段脂肪细胞(未分化0d、中期分化4d、接近完全分化8d)与原代肝细胞共培养。Western印迹法检测共培养后肝细胞内胰岛素信号通路的反应性;葡萄糖同位素标记方法检测肝细胞糖原合成能力。结果以未共培养的肝细胞为对照组,共培养后肝细胞内胰岛素受体底物-2酪氨酸磷酸化(Tyr612)(pIRS-2)水平及Akt磷酸化(Ser473)(pAkt)水平均显著下调;肝糖原合成能力明显降低;与较成熟脂肪细胞共培养后,肝细胞pIRS-2及pAkt水平与其他分化阶段组共培养比较下调明显,肝糖原合成能力随着脂肪细胞的成熟而明显降低。结论脂肪细胞可能诱导肝细胞发生胰岛素抵抗,肝细胞胰岛素信号通路的阻滞程度与脂肪细胞的分化程度呈正相关。

Objective To assess the effects of fat cells on the development of hepatic insulin resistance. Methods Hepatic cells were co-cultured with fat cells at various stages of differentiation and the effects of fat cells on insulin signal transduction and glycogen synthesis in hepatic cells were evaluated. Results Insulin-induced tyrosine phosphorylation of IRS-2 was significantly blocked. Insulin-regulated activation of Akt kinase and glycogen production in the hepatocytes were also reduced after co-culture, and the reduction was correlated with the differentiation of co-cultured fat cells. Conclusion These results suggest that adipocyte differentiation might induce insulin resistance in hepatocytes. Our study provided direct evidence of interaction between the adipocytes and hepatocytes in insulin signaling.