21 April 2018 : Laboratory Research
Valsartan Alleviates Insulin Resistance in Skeletal Muscle of Chronic Renal Failure Rats
Yang Wang1ABCE, Ri-bao Wei1AG*, Yue Yang12BCDE, Ting-Yu Su1C, Meng-Jie Huang1D, Ping Li1FG, Xiang-Mei Chen1FDOI: 10.12659/MSM.909910
Med Sci Monit 2018; 24: LBR2413-2419
Abstract
BACKGROUND: 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.
MATERIAL AND METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
Keywords: Insulin Resistance, Kidney Failure, Chronic, Muscle, Skeletal
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