褪黑素通过抑制ROS改善胰岛素抵抗HepG2细胞糖代谢

Melatonin Ameliorates Glucose Metabolism via Inhibiting ROS Generation in Insulin Resistant HepG2 Cells Induced by High Glucose and Insulin

目的探讨褪黑素(MLT)对胰岛素抵抗(IR)HepG2细胞葡萄糖代谢的影响及机制。方法培养HepG2细胞,高糖高胰岛素(25 mmol/L葡萄糖、1μmol/L胰岛素)诱导24h,建立IR细胞模型并给予MLT(1 nmol/L,10 nmol/L)处理。葡萄糖氧化酶法、蒽酮法和荧光探针法检测HepG2细胞的糖摄取、糖原含量及活性氧(ROS)产率。结果 HGI孵育HepG2细胞24 h后,细胞的葡萄糖摄取及糖原含量明显减少(P<0.01),ROS产率显著增加(P<0.01);而MLT处理增加了IR细胞葡糖糖的摄取(P<0.01)和糖原合成(P<0.05),降低ROS的水平(P<0.01)。结论 MLT可能通过抑制ROS的生成而改善氧化应激,从而促进胰岛素抵抗HepG2细胞葡萄糖的摄取和利用、增强其胰岛素敏感性。

Objective To investigate the effects of melatonin on glucose metabolism in high glucose and insulin-induced insulin resistant HepG2 cells. Methods Insulin resistant HepG2 cells were induced by high glucose and insulin （ HGI,25 mmol/L and 1 μmoL/L respectively） cocuhure for 24 h, and then melatonin was added. The uptake of glucose was measured by glucose oxidase method, anthrone method was used to detect the Glycogen synthesis and fluorescence probe was used to detect ROS production. Results HGI incubating led to significant decreases in insulin-stimulated glucose uptake and glycogen synthesis in HepG2 ceils （ P 〈 0.01 ）, but ROS production increased （ P 〈 0.01 ）. However, MLT treatment reversed the above state by increasing glucose uptake （P 〈 0.01 ） and glycogen synthesis （P 〈 0.05） ,inhibiting the generation of ROS（P 〈 0.01 ）. Conclusions MLT could improve oxidative stress by inhibiting the production of ROS, and thereby increase glucose utilization and improve insulin sensitivity of insulin resistance HepG2 ceils.