新型磺酰脲类化合物G004对胰岛素抵抗HepG2细胞模型糖代谢的影响

Effects of new sulfonylurea compound G004 on glycometabolism in insulin-resistance HepG2 cells

目的探讨新型磺酰脲类化合物G004对IR-HepG2细胞的糖代谢的影响。方法将HepG2细胞置于5×10-7mol/L胰岛素培养液中16h建立胰岛素抵抗模型(IR-HepG2),并观察G004对IR-HepG2细胞模型葡萄糖消耗量(GC)、细胞内糖原含量、与胰岛素协同作用、糖异生以及糖异生关键酶磷酸烯醇式丙酮酸羧激酶(PEPCK)活性的影响。结果与模型组相比,G004显著增加IR-HepG2细胞在高、中、低糖条件下的葡萄糖消耗量,并呈现出非胰岛素依赖性;增加IR-HepG2细胞内糖原含量;减少IR-HepG2细胞以乳酸为底物的糖异生量并下调细胞内PEPCK活性,本研究中未发现格列美脲对以乳酸为底物的糖异生以及关键酶PEPCK有明显抑制作用。结论G004可显著改善IR-HepG2细胞的糖代谢的作用。

[Objective] To investigate the effect of new suffonylurea compound G004 on glycometabolism in insulin-resistance HepG2 cells. [Methods] HepG2 cells were incubated with 5 ×10^-7 mol/L insulin for 16 h to establish insulin-resistance （IR- HepG2）. The effects of new sulfonylurea compound G004 on glucose consumption （GC）, synergic action of insulin, glycogen synthesis, gluconeogenesis and activity of PEPCK were tested in this model respectively. [Results] Compared with model group, G004 could noninsulin-dependently increase GC in insulin-resistance HepG2 ceils at high, medium and low levels of glucose respectively. It enhanced IR- HepG2 cells glycogen synthesis significantly. G004 inhinited gluconeogenesis from lactic acid and activity of PEPCK. However, this study showed glimepiride did not facilitate gluconeogenesis and PEPCK activity of HEPG2 cells obviously. [ Conclusion] Compound G004 had remarkable effect on improving glycometabolism in IR-HepG2 cells. Key words： glycometabolism; HepG2; insulin-resistance