摘要
目的探讨高浓度胰岛素和高浓度糖(高糖)共同作用诱导胰岛素抵抗的分子机理. 方法分离的大鼠脂肪细胞在5、25 mmol/L糖或加胰岛素(104 μU/ml)培养基中孵育24 h,然后测定糖的转运率、胰岛素受体(IR)、胰岛素受体底物 (IRS) 1/2的酪氨酸磷酸化,IRS 1/2,肌醇磷脂-3-激酶85亚单位(p85) 和蛋白激酶B(PKB)的蛋白表达及PKB活性. 结果高糖使这些细胞的糖摄取率、IR和IRS-1的酪氨酸磷酸化分别下降了69%、43%和52%,IRS-1蛋白表达下降61%及PKB活性降低42%.高胰岛素加重高糖的以上抑制作用 (与25 mmol/L葡萄糖组比较,P<0.05、P<0.01);高糖增加IRS-2 蛋白表达20.4%,高胰岛素对抗高糖的此作用. 结论高糖能诱导胰岛素抵抗,高胰岛素加重高糖的此作用.其作用机制与影响胰岛素信号通道各蛋白的磷酸化、表达及PKB活性等因素有关.
Objective To explore the molecular mechanism of high insulin and high glucose-induced insulin resistance. Methods Isolated rat adipocytes were cultured at 5 or 25 mmol/L glucose with or without insulin(104μU/ml)for 24 h. Then the glucose uptake, the phosphorylation of insulin receptor(IR), insulin receptor substrate (IRS)l/2, the protein expression of IRS-1 ,IRS-2,85 subunit of phosphatitylinositol 3-kinase (p85) and protein kinase B (PKB) as well as PKB activity were measured. Results These adipocytes treated with 25 mmol/L glucose showed that high glucose reduced glucose uptake, IR and IRS-1 phosphorylationby 69%,43% and 52% respectively, and depressed IRS-1 protein expression and PKB activity by 61% and 42% respectively. Combined treatment with high insulin and high glucose amplified the above suppression (compared with 25 mmol/L glucose group F<0. 05,P<0. 01). High glucose increased IRS-2 protein expression by 204%, but high insulin abolished its effect. Conclusion High glucose can induce insulin resistance, and high insulin can amplify its effect. The mechanism may be involved in their affecting the phosphorylation and expression of insulin signaling proteins as well as PKB activity.
出处
《中国糖尿病杂志》
CAS
CSCD
2003年第2期118-121,共4页
Chinese Journal of Diabetes
