摘要
目的研究血管紧张素II和坎地沙坦对小鼠骨骼肌细胞(C2C12)胰岛素敏感性的影响及其机制。方法C2C12诱导分化成熟后,分为对照组(C组)、模型组(M组:Ang II)、坎地沙坦低剂量组(Can1组:坎地沙坦0.1μM+Ang II)、坎地沙坦中剂量组(Can2组:坎地沙坦1μM+Ang II)、坎地沙坦高剂量组(Can3组:坎地沙坦10μM+Ang II)。各组细胞给予相应药物及胰岛素处理后,检测2-脱氧葡萄糖(2-NBDG)的摄取率,并用RT-PCR法和Western印记法分别检测各组细胞中磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)和胰岛素受体底物分子-1(ISR-1)的m RNA及蛋白表达水平。结果 M组摄取2-NBDG较C组明显降低(P<0.01),而Can3组摄取2-NBDG则较M明显增加(P<0.05)。M组ISR-1和Akt的m RNA表达较C组明显降低(P<0.01),Can2组及Can3组ISR-1、PI3K和Atk的m RNA表达较M组明显升高(P<0.05)。M组p-ISR-1和p-Akt蛋白表达较C组明显降低(P<0.01),Can2组及Can3组p-ISR-1和p-Akt较M组明显升高(P<0.05)。结论 Ang II通过下调胰岛素信号通路中重要因子ISR-1、Akt的m RNA及蛋白表达抑制胰岛素的生物学效应,引起骨骼肌细胞胰岛素抵抗;而坎地沙坦通过抑制Ang II的这种作用改善骨骼肌胰岛素抵抗。
Objective To investigate the effects of candesartan and angiotensin II on insulin sensitivity in C2C12 myotubes and discuss the possible mechanisms. Methods Mature C2C12 myotubes were divided into 5 groups：control（group C）,model（group M）,low dose candesartan（group Can1）,mild dose candesartan（group Can2） and high dose candersartan（group Can3）. After the intervention of angiotensin II and insulin,the uptake of 2-deoxyglucose（2-NBDG） by C2C12 myotubes was measured in each group.The m RNA and protein expression of PI3 K,ISR-1 and Akt were measured with RT-PCR and Western blotting assay. Results Compared with group C,the uptake of 2-NBDG significantly decreased in group M（P〈0.01）,while the m RNA and protein expression of I SR-1 and Atk in group M significantly decreased（P〈0.01）. Compared with group M,the uptake of 2-NBGD increased significantly in group Can3（P〈0.05）. The m RNA expression of ISR-1,PI3 K and Akt in groups Can2 and Can3 significantly increased（ P〈0.01）,（P〈0.05） compared with group M,and the protein express of ISR-1 and Akt significantly increased（P〈0.01）,（P〈0.05）.Conclusion Angiotensin II can cause the insulin resistance of the skeletal muscle cells by down regulation the m RNA and protein expression of insulin signal pathway factors such as ISR-1 and Akt. Candesartan can improve skeletal muscle cells insulin resistance by reverse the effect of Ang II on insulin signal PI3K/Akt pathway.
出处
《中华保健医学杂志》
2015年第1期21-23,共3页
Chinese Journal of Health Care and Medicine
基金
北京市自然科学基金项目(7122171)
