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Horm Metab Res 2010; 42(9): 637-642
DOI: 10.1055/s-0030-1253373
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

The Decreased Expression of Peroxisome Proliferator-activated Receptors δ (PPARδ) is Reversed by Digoxin in the Heart of Diabetic Rats

S. C. Fan1 , B. C. Yu2 , Z. C. Chen3 , 4 , L. J. Chen2 , H. H. Chung2 , J. T. Cheng2 , 4
  • 1Department of Internal Medicine, Zhongxing Branch of Taipei City Hospital, Taipei City, Taiwan, R. O. C.
  • 2Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R. O. C.
  • 3Department of Cardiology, Chi-Mei Medical Center, Yong Kang City, Tainan Shen, Taiwan, R. O. C.
  • 4Department of Medical Research, Chi-Mei Medical Center, Yong Kang City, Tainan Shen, Taiwan, R. O. C.
Further Information

Publication History

received 27.01.2010

accepted 31.03.2010

Publication Date:
05 May 2010 (online)

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Abstract

The present study is designed to investigate the role of peroxisome proliferator-activated receptors δ (PPARδ) in the action of digoxin in diabetic rats showing cardiac hypertrophy. We used Wistar rats to induce diabetes by injection of streptozotocin (STZ-rat) and examined the effect of digoxin on PPARδ expression in these hyperglycemic rats (STZ-rat) at 10 weeks later. We measured the changes of body weight, water intake, and food intake in three groups of age-matched rats; the vehicle treated normal control (Wistar rats), the vehicle treated STZ-rats, and the digoxin-treated STZ-rats. Cardiac output, heart rate, and blood pressure in addition to plasma insulin or glucose level were also determined. The mRNA and protein levels of PPARδ were measured using Northern and Western blotting, respectively. Cardiac output, heart rate, and blood pressure were markedly reduced while food intake, water intake, and blood glucose were raised in STZ-rats showing lower body weight and plasma insulin as compared with the vehicle-treated controls. After a 20-day of digoxin treatment, cardiac output was raised in STZ-rats but the diabetic parameters were not modified. The PPARδ expressions, both mRNA and protein, were markedly elevated in the hearts of STZ-rats by digoxin treatment. The related signals with PPARδ, such as carnitine palmitoyltransferase 1B (CPT1B), acetyl-coenzyme A, carboxylase alpha (ACC1), fatty acid synthase (FAS), and troponin I, were also raised. The increase of cardiac output by digoxin was reversed by the combined treatment with PPARδ antagonist GSK0660. Thus, we suggest a new finding that PPARδ is involved in digoxin induced cardiac inrotropic action.

Key words

digoxin - cardiac output - PPARδ - heart - diabetic rat

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Correspondence

Prof. J. T. Cheng

Department of Medical

Research

Chi-Mei Medical Center

Yong Kang City

Taiwan 70301

R. O. C.

Phone: +886/6/331 8516

Fax: +886/6/238 6548

Email: m980103@mail.chimei.org.tw

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