The decreased expression of peroxisome proliferator-activated receptors delta (PPARdelta) is reversed by digoxin in the heart of diabetic rats.
The present study is designed to investigate the role of peroxisome proliferator-activated receptors delta (PPARdelta) 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 PPARdelta 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 PPARdelta 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 PPARdelta expressions, both mRNA and protein, were markedly elevated in the hearts of STZ-rats by digoxin treatment. The related signals with PPARdelta, 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 PPARdelta antagonist GSK0660. Thus, we suggest a new finding that PPARdelta is involved in digoxin induced cardiac inrotropic action.
Fan
S C
SC
Department of Internal Medicine, Zhongxing Branch of Taipei City Hospital, Taipei City, Taiwan, ROC.
Yu
B C
BC
Chen
Z C
ZC
Chen
L J
LJ
Chung
H H
HH
Cheng
J T
JT
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004077:Digoxin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D047494:PPAR delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013450:Sulfones / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D019210:Troponin I / Q000378:metabolism
C529769:GSK0660; D047494:PPAR delta; D013450:Sulfones; D013876:Thiophenes; D019210:Troponin I; D013311:Streptozocin; D004077:Digoxin