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

© Georg Thieme Verlag KG Stuttgart · New York

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
Further Information

Publication History

received 30.10.2010

accepted 19.01.2011

Publication Date:
01 March 2011 (online)

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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

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1 These two authors contributed equally to the work.

Correspondence

C.-J. ChangMD 

Department of Family Medicine

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