Pioglitazone but Not Glibenclamide Improves Cardiac Expression of Heat Shock Protein 72 and Tolerance Against Ischemia/Reperfusion Injury in the Heredity Insulin-Resistant Rat

• Published in: Diabetes (New York, N.Y.) Vol. 55; no. 8; pp. 2371 - 2378
• Main Authors: TANIGUCHI, Yayoi, OOIE, Tatsuhiko, TAKAHASHI, Naohiko, SHINOHARA, Tetsuji, NAKAGAWA, Mikiko, YONEMOCHI, Hidetoshi, HARA, Masahide, YOSHIMATSU, Hironobu, SAIKAWA, Tetsunori
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2006
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Care and treatment; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes research; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fever; Glucose Tolerance Test; Glyburide - therapeutic use; Health aspects; HSP72 Heat-Shock Proteins - analysis; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin resistance; Insulin Resistance - genetics; Kinetics; Male; Medical sciences; Myocardial Reperfusion Injury - prevention & control; Myocardium - chemistry; Myocardium - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Inbred OLETF; Reperfusion injury; Thiazolidinediones - therapeutic use; Ventricular Function, Left - drug effects; Endocrinopathy; Sulfanilamide derivatives; Pancreatic hormone; Rat; Diabetes mellitus; Pioglitazone; Rodentia; Tolerance; Cardiovascular disease; Thiazolidinedione derivatives; Insulin; Vertebrata; Mammalia; Ischemia; Animal; Sulfonylureas; Heat shock protein; Glibenclamide
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db06-0268

Pioglitazone but Not Glibenclamide Improves Cardiac Expression of Heat Shock Protein 72 and Tolerance Against Ischemia/Reperfusion Injury in the Heredity Insulin-Resistant Rat Yayoi Taniguchi 1 , Tatsuhiko Ooie 1 , Naohiko Takahashi 2 , Tetsuji Shinohara 2 , Mikiko Nakagawa 1 , Hidetoshi Yonemochi 1 , Masahide Hara 2 , Hironobu Yoshimatsu 2 and Tetsunori Saikawa 1 1 Department of Cardiovascular Science, Faculty of Medicine, Oita University, Oita, Japan 2 Department of Internal Medicine 1, Faculty of Medicine, Oita University, Oita, Japan Address correspondence and reprint requests to Naohiko Takahashi, MD, PhD, Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Yufu, Oita 879-5593, Japan. E-mail: takanao{at}med.oita-u.ac.jp Abstract We tested the hypothesis that pioglitazone could restore expression of heat shock protein (HSP)72 in insulin-resistant rat heart. At 12 weeks of age, male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control (LETO) rats were treated with pioglitazone (10 mg · kg −1 · day −1 ) or glibenclamide (5 mg · kg −1 · day −1 ) for 4 weeks. Thereafter, hyperthermia (43°C for 20 min) was applied. In response to hyperthermia, the activation of serine/threonine kinase Akt depending on phosphatidylinositol 3 (PI3) kinase was necessary for cardiac expression of HSP72. Hyperthermia-induced activation of Akt and HSP72 expression were depressed in OLETF rat hearts. Pioglitazone but not glibenclamide improved insulin sensitivity in OLETF rats, which was associated with the restoration of Akt activation and HSP72 expression. In experiments with isolated perfused heart, reperfusion-induced cardiac functional recovery was suppressed in OLETF rat hearts, which was improved by pioglitazone but not glibenclamide. Our results suggest that PI3 kinase–dependent Akt activation, an essential signal for HSP72 expression, is depressed in the heart in insulin-resistant OLETF rats, and the results suggest also that the restoration of HSP72 expression and tolerance against ischemia/reperfusion injury by treatment with pioglitazone might be due to an improvement of insulin resistance, leading to restoration of impaired PI3 kinase–dependent Akt activation in response to hyperthermia. CPP, coronary perfusion pressure GGA, geranylgeranylacetone HSP, heat shock protein LVDP, left ventricular developed pressure OGTT, oral glucose tolerance test PI3, phosphatidylinositol 3 PPAR-γ, peroxisome proliferator–activated receptor-γ STZ, streptozotocin Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted May 22, 2006. Received February 25, 2006. DIABETES