褪黑素通过Akt抑制胰岛素抵抗HepG2细胞糖内生

目的探讨褪黑素(melatonin,MLT)对胰岛素抵抗(insulin resistance,IR)肝HepG2细胞葡萄糖内生的影响及其机制。方法HepG2 IR细胞模型采用高糖(25 mmol·L-1)联合高胰岛素(1μmol·L-1)培养诱导建立。MLT(10 nmol·L-1)处理模型细胞6 h后检测糖消耗及糖原含量,GSK-3β、Akt和FoxO1蛋白磷酸化水平检测采用Western blot,免疫荧光法检测FoxO1蛋白核外排情况。结果IR HepG2细胞经MLT处理后,葡萄糖的摄取和糖原合成增加,p-GSK-3β和p-Akt蛋白水平分别增高约66%和48%,FoxO1磷酸化水平明显提高且细胞质含量增加。结论MLT可能通过Akt/GSK-3β及Akt/FoxO1信号通路促进胰岛素抵抗HepG2细胞的糖原合成和抑制糖异生,从而改善糖代谢。

Melatonin inhibits endogenous glucose via activation of Akt in insulin resistant HepG2 cells

Aim To study the effects of melatonin on glucose output in insulin resistant HepG2 cells and the related mechanism.Methods Insulin resistant HepG2 cells were induced by high glucose and insulin(HGI)(25 mmol·L-1 and 1μmol·L-1 respectively)co-culture for 24 h,and then melatonin(10 nmol·L-1)was supplied.The glucose uptake and the glycogen content were measured.Levels of protein p-Akt,p-FoxO1 as well as p-GSK-3βwere evaluated by Western blot.The nuclear export of FoxO1 and its intracellular localization were detected by immunofluorescence.Results HGI incubation led to significant decrease in insulin-stimulated glucose uptake and glycogen synthesis in HepG2 cells(P<0.01).However,melatonin reversed these inhibitory effects by increasing glucose uptake and glycogen synthesis significantly(P<0.01).The results also showed that melatonin not only up-regulated levels of protein p-GSK-3β,p-Akt and p-FoxO1 but also promoted cytoplasm translocation of FoxO1.Conclusions Melatonin could regulate glycogenesis and gluconeogenesis in insulin resistant HepG2 cells via Akt/GSK-3βand Akt/FoxO1 pathway.It thus suppresses the endogenous glucose output and improves the glucose metabolism.