Valsartan Alleviates Insulin Resistance in Skeletal Muscle of Chronic Renal Failure Rats.
Valsartan Alleviates Insulin Resistance in Skeletal Muscle of Chronic Renal Failure Rats.
复制标题
DOI：
10.12659/msm.909910
复制
发表时间：
2018-04-21
期刊：
影响因子：
--
通讯作者：
Chen XM
中科院分区：
文献类型：
--
作者：
Wang Y;Wei RB;Yang Y;Su TY;Huang MJ;Li P;Chen XM
关于慢性肾脏病（CKD）患者胰岛素抵抗（IR）的研究很少，其确切机制仍不清楚。在本研究中，我们探讨了 IR 与慢性肾衰竭 (CRF) 的分子机制以及缓解 CRF 患者 IR 的干预措施。分别通过5/6肾切除和尿素刺激C2C12细胞建立CRF的体内和体外模型。基于CRF模型，建立血管紧张素II（Ang II）组和缬沙坦组，观察药物干预对IR的影响。采用蛋白质印迹法检测 IRS-1 和 Akt（胰岛素信号传导通路中的 2 个关键蛋白）的表达和磷酸化。尿素刺激和5/6肾切除均引起骨骼肌细胞葡萄糖摄取障碍（P<0.01）。 Ang II组骨骼肌IR加重（P<0.05），缬沙坦组减轻（P<0.01）。无论采用何种实验方法（体内或体外），模型组IRS-1和Akt的酪氨酸磷酸化均显着低于假手术组/对照组（P<0.01），丝氨酸磷酸化显着高于假手术组/对照组（P<0.01）。与模型组相比，额外添加Ang II会加重磷酸化异常（P<0.05）；相反，额外的缬沙坦在一定程度上减轻了异常磷酸化（P<0.05）。 CRF 存在时存在骨骼肌胰岛素抵抗。 Ang II 可以加剧这种现象，而缬沙坦可以部分缓解这种现象。 CRF 患者 IR 的机制之一可能与 IRS-PI3k-Akt 通路中关键蛋白的磷酸化水平改变有关。
Studies on insulin resistance (IR) in chronic kidney disease (CKD) patients are rare, and its exact mechanism remains unclear. In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to alleviate IR in patients with CRF. In vivo and in vitro models of CRF were established by 5/6 nephrectomy and urea stimulation C2C12 cells, respectively. Based on the CRF model, angiotensin II (Ang II) and valsartan groups were established to observe the effect of drug intervention on IR. Western blot assays were performed to detect the expression and phosphorylation of IRS-1 and Akt, which are 2 critical proteins in the insulin signaling pathway. Both urea stimulation and 5/6 nephrectomy induced glucose uptake disorder in skeletal muscle cells (P<0.01). Skeletal muscle IR was aggravated in the Ang II group (P<0.05) but alleviated in the valsartan group (P<0.01). Regardless of the experimental method (in vivo or in vitro), tyrosine phosphorylation of IRS-1 and Akt were significantly lower (P<0.01) and serine phosphorylation was significantly higher (P<0.01) in the model group than in the sham/control group. Compared to the model group, additional Ang II aggravated abnormal phosphorylation (P<0.05); conversely, additional valsartan alleviated abnormal phosphorylation to some extent (P<0.05). There is skeletal muscle insulin resistance in the presence of CRF. This phenomenon can be aggravated by Ang II and partially relieved by valsartan. One of the mechanisms of IR in CRF patients may be associated with the critical proteins in the IRS-PI3k-Akt pathway by changing their phosphorylation levels.
登录
查看更多内容
影响因子：
3.8
作者：
Lastra, Guido;Santos, Fernando R.;Henriksen, Erik J.
通讯作者：
Henriksen, Erik J.
影响因子：
15.9
作者：
Folli, F;Kahn, CR;Feener, EP
通讯作者：
Feener, EP
影响因子：
3
作者：
Canbakan, Mustafa;Sahin, Gulizar Manga
通讯作者：
Sahin, Gulizar Manga
影响因子：
7.7
作者：
Griffin, ME;Marcucci, MJ;Shulman, GI
通讯作者：
Shulman, GI
影响因子：
120.7
作者：
Lakka, HM;Laaksonen, DE;Salonen, JT
通讯作者：
Salonen, JT