Elevated Retinol Binding Protein 4 Contributes to Insulin Resistance in Spontaneously Hypertensive Rats

H.-Y. Ou; H.-T. Wu; Y.-C. Yang; J.-S. Wu; J.-T. Cheng; C.-J. Chang

doi:10.1055/s-0031-1271746

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2011; 43(5): 312-318
DOI: 10.1055/s-0031-1271746

Original Basic

Elevated Retinol Binding Protein 4 Contributes to Insulin Resistance in Spontaneously Hypertensive Rats

H.-Y. Ou¹ ^, ² , H.-T. Wu³ , Y.-C. Yang⁴ , J.-S. Wu⁴ , J.-T. Cheng⁵ ^, ⁶ ^, [*] , C.-J. Chang⁴ ^, [*]

¹Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
²Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan
³Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
⁴Department of Family Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan
⁵Department of Medical Research, Chi-Mei Medical Center, Yong Kang City, Tainan, Taiwan
⁶Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan, Taiwan

Abstract

Retinol binding protein 4 (RBP4) is an adipokine secreted by adipose tissue and liver and contributes to insulin resistance (IR) in animals. Although several human studies indicated that RBP4 is positively correlated with blood pressure and is elevated in untreated hypertensive subjects, the role of RBP4 in IR of hypertensive animals still remains obscure. In this study, spontaneously hypertensive rats (SHR) were used to investigate the relationship between RBP4 levels and IR. We found that at 7 weeks old, SHR had significantly increased plasma RBP4 levels and RBP4 expression in liver and epididymal adipose tissue accompanied by worsening of IR as compared with Wistar-Kyoto (WKY) control rats. Administration of fenretinide in SHR to increase urinary RBP4 excretion significantly decreased plasma RBP4 levels and improved IR. Moreover, treatment with valsartan markedly reduced blood pressure, circulating RBP4 and adiponectin levels, and IR in SHR. Valsartan also reversed the increase of hepatic gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and the decrease of type 4 glucose transporter (GLUT4) in adipose tissue. In conclusion, these results suggest that RBP4 contributes, at least partly, to the pathogenesis of IR in SHR. Furthermore, the decrease of blood pressure caused by valsartan not only decreased RBP4 levels, but also improved IR in SHR.

Key words

diabetes - valsartan - insulin resistance - retinol binding protein 4 - spontaneously hypertensive rats

Full Text

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1 These two authors contributed equally to the work.

Correspondence

C.-J. ChangMD

Department of Family Medicine

National Cheng Kung University

Hospital

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