替米沙坦阻断血管紧张素Ⅱ作用促进骨骼肌细胞糖摄取

Telmisartan promotes glucose uptake in skeletal muscle cell by blocking angiotensin Ⅱ

目的研究替米沙坦和血管紧张素Ⅱ对小鼠骨骼肌成肌细胞C2C12的葡萄糖摄取和胰岛素信号传导途径的影响,探讨替米沙坦影响糖代谢的可能机制。方法诱导成熟的C2C12细胞分为对照组(C组)、胰岛素组(Ins组)、胰岛素+血管紧张素Ⅱ组(Ins+AngⅡ组)、胰岛素+血管紧张素Ⅱ+替米沙坦组(Ins+AngⅡ+Tel组)。经相应药物干预后测定细胞2-脱氧葡萄糖摄入率,并用Western印迹法检测磷脂酰肌醇3激酶(PI3-K)p85α、丝氨酸/苏氨酸蛋白激酶(AKT)1、P38、胞外信号调节激酶(ERK)1蛋白表达。结果Ins组胰岛素信号转导通路的信号分子PI3-Kp85α、AKT1、P38、胞外信号调节激酶(ERK1)的蛋白表达均较C组显著升高(P值均<0.05);Ins+AngⅡ组PI3-Kp85α和AKT1的蛋白表达较Ins组显著下降(P值均<0.05),而两组间P38和ERK1蛋白表达的差异则无统计学意义(P值均>0.05);Ins+AngⅡ+Tel组PI3-Kp85α和AKT1的蛋白表达较Ins+AngⅡ组显著增加(P值均<0.05),两组P38和ERK1蛋白表达的差异则无统计学意义(P值均>0.05)。结论替米沙坦逆转血管紧张素Ⅱ对骨骼肌细胞葡萄糖吸收和抑制胰岛素信号转导PI3-K途径的作用,可能是其影响糖代谢的机制之一。

Objective To investigate the effect of telmisartan and angiotensin Ⅱ on glucose uptake and insulin signal pathway in C2C12 myotubes, so as to discuss the possible mechanism of telmisartan on glucose metabolism. Methods The mature myotubes were divided into the following 4 groups., control （group C）, insulin （ Ins group）, insulin ＋ angtension Ⅱ （Ins ＋ Ang Ⅱ group） and Insulin ＋ angtension Ⅱ ＋ telmisartan（Ins ＋ Ang Ⅱ ＋ Tel group）. The uptake of 2-deoxyglucose （2-DOG） by C2C12 myotubes was assayed after treatment in each group. The protein expressions of P13-K p85α, AKT1, P38 and ERK1 were measured by Western blotting assay. Results The 2-DOG uptake was significantly decreased and the expressions of P13-K p85α and AKT1 in C2C12 myotubes were significantly decreased （P〈0.05） in Ins ＋ Ang Ⅱ group （P〈0.01）compared with Ins group. The protein expressions of P13-K p85α and AKT1 in Ins ＋ Ang Ⅱ group were significantly lower than those in the Ins group （P〈0.05）; while the 2 groups had similar P38 and ERK1 expression. The protein expression of P13-K p85α and AKT1 in Ins＋ Ang Ⅱ ＋ Tel group were significantly higher than that of the Ins＋ Ang Ⅱ group; while the expression of P38 and ERK1 was similar between the 2 groups. Conclusion Telmisartan can reverse the effect of angtensin Ⅱ on the 2-DOG uptake and insulin signal P13-K pathway in the skeletal muscle cells, which might be one of the mechanisms responsible for the influence of telmisartan on glycometabolism. （Shanghai Med J, 2009, 32： 418-420）