Reduced cardiotropic response to insulin in spontaneously hypertensive rats: role of peroxisome proliferator-activated receptor-gamma-initiated signaling.

Authors

• Haifeng Zhang
• Jia Li
• Rong Li
• Quanjiang Zhang
• Heng Ma
• Qiuhe Ji
• Wenyi Guo
• Haichang Wang
• Bernard L Lopez
• Theodore A Christopher
• Xinliang Ma
• Feng Gao

Publication/Presentation Date

3-1-2008

Abstract

OBJECTIVES: Vascular insulin resistance plays a crucial pathogenic role in the development of genetic hypertension. However, it is not known whether hypertension-associated myocardial insulin resistance also exists, and whether this is involved in the development of related diseases, such as hypertensive heart failure. The present study aimed to determine whether hypertension-associated myocardial insulin resistance exists, in addition to any underlying mechanism.

METHODS: Ventricular myocytes were enzymatically isolated from male Wistar-Kyoto (WKY) rats or spontaneously hypertensive rats (SHR) and myocyte shortening and intracellular Ca2+ transient were assessed, as was any signaling mechanism.

RESULTS: Compared with WKY rats, insulin-stimulated myocardial glucose uptake was blunted in SHR. More importantly, the positive inotropic effect of insulin was significantly reduced in SHR myocytes. Moreover, peroxisome proliferator-activated receptor (PPAR)gamma and phosphatidylinositol 3 (PI-3) kinase p85 expression and insulin-induced Akt phosphorylation were reduced in SHR cardiomyocytes, but were markedly restored when animals were treated with rosiglitazone for 14 days. Pretreatment with an Akt inhibitor abolished the inotropic effect induced by insulin in rosiglitazone-treated SHR cardiomyocytes.

CONCLUSIONS: The data obtained demonstrate that insulin resistance exists in SHR cardiomyocytes as manifested by both reduced insulin-stimulated glucose uptake and an impaired contractile response to insulin, which is attributable to decreased PPARgamma expression and subsequent impairment in PI-3 kinase/Akt signaling.

Volume

26

Issue

3

First Page

560

Last Page

569

ISSN

0263-6352

Published In/Presented At

Zhang, H., Li, J., Li, R., Zhang, Q., Ma, H., Ji, Q., Guo, W., Wang, H., Lopez, B. L., Christopher, T. A., Ma, X., & Gao, F. (2008). Reduced cardiotropic response to insulin in spontaneously hypertensive rats: role of peroxisome proliferator-activated receptor-gamma-initiated signaling. Journal of hypertension, 26(3), 560–569. https://doi.org/10.1097/HJH.0b013e3282f343e1

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

18300869

Department(s)

Administration and Leadership

Document Type

Article