Pioglitazone reverses down-regulation of cardiac PPAR{gamma} expression in Zucker diabetic fatty rats

Journal Article · Fri Apr 08 04:00:00 EDT 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.02.029· OSTI ID:20630929

Pelzer, Theo ^[1]; Jazbutyte, Virginija ^[1]; Arias-Loza, Paula Anahi ^[1]; Segerer, Stephan ^[1]; Lichtenwald, Margit ^[1]; Law, Marilyn P ^[2]; Schaefers, Michael ^[2]; Ertl, Georg ^[1]; Neyses, Ludwig ^[3]

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1. Department of Medicine, University of Wuerzburg (Germany)
2. Department of Nuclear Medicine, University Hospital, Muenster (Germany)
3. Division of Cardiology University of Manchester (United Kingdom)

Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPAR{gamma} in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPAR{gamma} agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPAR{gamma}, glucose transporter-4 and {alpha}-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPAR{gamma}, glut-4, and {alpha}-MHC expression levels in diabetic ZDF rats. Cardiac [{sup 18}F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPAR{gamma} agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPAR{gamma} expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin.

• OSTI ID: 20630929
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 329; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
FLUORINE 18
FLUORODEOXYGLUCOSE
GENE REGULATION
GENES
GLUCOSE
HEART
HOMEOSTASIS
HYPERGLYCEMIA
HYPERTROPHY
INSULIN
METABOLISM
MYOSIN
RATS
RECEPTORS
UPTAKE