过氧化物酶体增殖激活受体γ或α在改善HepG2细胞糖代谢中的作用

目的：探讨过氧化物酶体增殖激活受体γ（PPAR-γ）或α（PPAR-α）激动剂改善HepG2细胞胰岛素抵抗的机制。方法：体外培养人肝癌细胞系HepG2细胞并用棕榈酸处理造成胰岛素抵抗模型,分别给予或PPAR-γ激动剂吡格列酮或高选择性PPAR-α激动剂WY14643处理,酶法测定葡萄糖的消耗量和糖酵解产物;同时定量PCR测定PPAR-γ、PPAR-α及糖酵解基因的表达变化。结果：吡格列酮增加胰岛素抵抗的HepG2细胞葡萄糖消耗,诱导糖酵解糖相关基因表达上调,促进糖酵解产物生成。WY14643部分改善胰岛素抵抗,对糖酵解相关基因表达及糖酵解产物水平没有显著影响。结论：PPAR-γ激动剂可能通过促进糖酵解改善HepG2细胞的胰岛素抵抗。

Roles of peroxisome proliferator-activated receptors in glucose metabolism in HepG2 cells

Objective：To characterize the mechanisms of peroxisome proliferator-activated receptors（PPAR）γ or α agonists in improving insulin resistance of human hepatoma cells.Methods：The model of insulin resistance was established with HepG2 cells cultured at high concentrations of palmitate.Insulin resistant HepG2 cells were treated with the PPAR-γ agonist pioglitazone or the PPAR-α agonist WY14643.Quantification of glucose consumption and glycolysis products pyruvate and lactate were performed.Quantitative RT-PCR was employed to analyze mRNA expression of PPAR-γ/α and glycolysis related genes.Results：Palmitate treatment decreased glucose consumption of HepG2 cells and induces insulin resistance.Pioglitazone increased glucose consumption of both normal and insulin resistant HepG2 cells.It induced an up-regulation of glycolysis related gene expression and strongly increased glycolysis reflected by elevated pyruvate and lactate production.WY14643 slightly increased glucose consumption of insulin resistant HepG2 cells,but had no effect on glycolysis gene expression.Conclusion：PPAR-γ or PPAR-α can enhance glucose metabolism in HepG2 cells through different mechanisms.PPAR-γ probablely improver insulin resistance of HepG2 cells through increasing glycolysis.