Myocardial remodeling in rats with metabolic syndrome: role of Rho-kinase mediated insulin resistance.
Insulin resistance (IR) plays a critical role in metabolic syndrome (MS). Previous studies have demonstrated that activated ROCK is increased in MS patients. However, the effect of Rho-kinase (ROCK) on IR has not been definitely determined. Thus, the aims of the present study were to determine whether ROCK activation induces IR or affects myocardial structure and function, as well as the possible mechanisms underlying this process. Wistar rats fed high fat, high glucose and high salt diet sewed as model of MS and we used transmission electron microscopy, echocardiogram technology, and terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling staining to identify any myocardial damage. The protein levels of MYPT-1 (characteristic of ROCK activation), IRS-1 and AKT were analyzed by immunohistochemistry and Western blotting. In hearts from MS rats, we found increased protein levels of phospho-MYPT-1 and phospho-IRS-1 (Ser307) and decreased phospho-AKT compared to levels in normal rats. In conclusion, the results suggest that ROCK-mediated IR is involved in the development of myocardial impairments in MS rats and that this effect is mediated probably via the IRS-1/PI3-kinase/AKT pathway.
Department of Emergency, Shandong University Qilu Hospital, Jinan, Shandong China.
Chuan-Bao
CB
Li
Xiao-Xing
XX
Li
Yu-Guo
YG
Chen
Hai-Qing
HQ
Gao
Cheng-Mei
CM
Bao
Xiang-Qun
XQ
Liu
Pei-Li
PL
Bu
Juan
J
Zhang
Yun
Y
Zhang
Xiao-Ping
XP
Ji
D000818:Animals; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology; D020257:Ventricular Remodeling; D054460:rho-Associated Kinases / Q000378:metabolism*
D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1