【摘要】 目的研究游离脂肪酸(FFA)诱导人肝癌细胞(HepG2)产生胰岛素抵抗及其分子机理。方法用含0.25 mmol/L的软脂酸(软脂酸组)或100 nmol/L胰岛素(高胰岛素组)的DMEM培养基培养HepG2细胞,再用100 nmol/L胰岛素刺激后,测定其培养液中的葡萄糖浓度、细胞内的糖原含量以及胰岛素受体底物2(IRS-2)的蛋白水平。加入磷酯酰肌醇3激酶(PI3K)的抑制剂wortmannin,再次检测IRS-2的蛋白水平。结果软脂酸组和高胰岛素组培养液中葡萄糖含量明显高于正常对照组(P<0.05),而细胞内糖原含量显著减少(P<0.01)。软脂酸组胰岛素刺激的IRS-2蛋白水平显著低于正常对照组(P<0.01)。用wortmannin处理后,软脂酸组中的IRS-2蛋白水平差异无显著意义(P>0.05),而正常细胞组中IRS-2蛋白水平差异有显著意义(P<0.01)。结论0.25mmol/L的软脂酸培养24 h后,HepG2细胞可产生胰岛素抵抗,且胰岛素信号转导途径存在障碍;PI3K是胰岛素信号转导途径中的关键调节点,可能IRS-2和一些PI3K相关分子缺陷与游离脂肪酸诱导的肝胰岛素抵抗的形成有关。更多还原

【Abstract】 Objective To explore free fatty acid-induced insulin resistance and its molecular mechanism in HepG2 cell.Methods HepG2 cells were incubated in DMEM medium with palmitate(0.25mmol/L) or insulin(100nmol/L) before the cells were stimulated with 100nmol/L insulin.Glucose concentration in medium,glycogen contents and protein level of IRS-2 were measured,(respectively) before and after adding wortmannin(PI3K inhibitor).(Results)In palmitate and insulin treatment groups,glucose concentration was significantly increased(P<0.05), glycogen contents and protein level of IRS-2 were significantly decreased compared with those in control group(P<0.01).Before and after wortmannin intervention,protein level of(IRS-2) was not significantly different in palmitate group(P>0.05),which was markedly different in normal group(P<0.01).Conclusion(After) HepG2 cells were incubated with palmitate,glucose metablism,gluconeogenesis,glycogenesis and glycogenlysis were affected by palmitate.Insulin resistance was induced because of the impairment of insulin receptor singling.Defects of IRS-2 and some PI3K-associated molecules might be responsible for the occurence of free fatty acid-induced insulin resistance.更多还原