Cited by 170Cardiac Ischemia and ReperfusionCardiovascular Function and Risk FactorsDiabetes Treatment and Management

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Rosiglitazone Treatment in Zucker Diabetic Fatty Rats Is Associated With Ameliorated Cardiac Insulin Resistance and Protection From Ischemia/Reperfusion-Induced Myocardial Injury

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Yue, Tian-Li, Bao, Weike, Gu, Juan-Li, Cui, Jianqi, Tao, Ling, Ma, Xin-Liang, Ohlstein, Eliot H., Jucker, Beat M.·2005·Diabetes

DOI 10.2337/diabetes.54.2.554

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Abstract

The mechanism responsible for the enhanced myocardial susceptibility to ischemic insult in patients with type 2 diabetes is not clear. The present study examines the effect of rosiglitazone treatment on cardiac insulin sensitization and its association with cardioprotection from ischemia/reperfusion injury in an animal model of diabetes. Male Zucker diabetic fatty (ZDF) rats were treated with rosiglitazone (3 mg · kg−1 · day−1 orally) or vehicle for 8 days before undergoing 30 min of coronary artery ligation, followed by reperfusion for 4 h (apoptosis) or 24 h (infarction). Rosiglitazone reduced the blood levels of glucose, triglycerides, and free fatty acids; enhanced cardiac glucose oxidation; and increased Akt phosphorylation (Akt-pS473) 2.1-fold and Akt kinase activity 1.8-fold in the ischemic myocardium. The phosphorylation of two downstream targets of Akt, glycogen synthase kinase-3β and FKHR (forkhead transcription factor), was also enhanced by 2- and 2.9-fold, respectively. In rosiglitazone-treated rats, the number of apoptotic cardiomyocytes and the myocardial infarct size were decreased by 58 and 46%, respectively, and the myocardial contractile dysfunction was improved. Blockade of the insulin-Akt signaling pathway by wortmannin in the 8-day rosiglitazone-treated ZDF rats resulted in a markedly diminished cardioprotective effect of rosiglitazone. In addition, 8-day rosiglitazone treatment in Zucker lean rats or 2-day rosiglitazone treatment in ZDF rats, both of which showed no change in whole-body insulin sensitivity, resulted in a significant reduction in cardiac infarct size, but to a lesser degree when compared with that observed in 8-day rosiglitazone–treated ZDF rats. These results suggest that chronic treatment with rosiglitazone protects the heart against ischemia/reperfusion injury in ZDF rats, and that the enhanced cardiac protection observed after rosiglitazone treatment might be attributable in part to an improvement in cardiac insulin sensitivity.

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Authors: Yue, T.-L., Bao, W., Gu, J.-L., Cui, J., Tao, L., Ma, X.-L., Ohlstein, E. H., & Jucker, B. M.
Affiliations: From the Department of Investigative and Cardiac Biology, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania
GlaxoSmithKline (United States) (US)
ORCID: Bao, Weike
Cui, Jianqi
Tao, Ling
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2005-02-01
Volume: 54
Issue: 2
Pages: 554-562
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.54.2.554
OpenAlex: W2154626866
Cited by: 170
References: 41
Citations by year: 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 10 · 2012: 14
FWCI: 13.37
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: rosiglitazone, cardiac insulin resistance, insulin sensitization, myocardial ischemia-reperfusion injury, type 2 diabetes, Zucker diabetic fatty rats, Akt signaling, glycogen synthase kinase-3β, forkhead transcription factor, cardiomyocyte apoptosis, myocardial infarct size, myocardial contractile dysfunction, wortmannin, PPARγ agonists
MeSH terms: Rosiglitazone, Administration, Oral, Animals, Blood Glucose, Coronary Vessels, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Heart, Hypoglycemic Agents, Insulin Resistance, Male, Myocardial Infarction, Myocardium, Rats, Zucker, Triglycerides, Myocardial Reperfusion Injury, Thiazolidinediones, Rats

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Rosiglitazone Treatment in Zucker Diabetic Fatty Rats Is Associated With Ameliorated Cardiac Insulin Resistance and Protection From Ischemia/Reperfusion-Induced Myocardial Injury

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