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Rosiglitazone Induces Cardiac Protein Kinase C beta2 Over‐expression And Increases Ventricular Mass in Type 2 Diabetic db/db Mice
Author(s) -
Xia Zhengyuan,
Carroll Rogayah,
Wang Fang,
Severson David L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb378
Subject(s) - protein kinase c , medicine , endocrinology , rosiglitazone , heart failure , protein kinase a , protein kinase b , diabetes mellitus , chemistry , phosphorylation , biochemistry
Rosiglitazone (RSG) treatment in type 2 diabetes has been associated with increased incidence and worsening of heart failure, but the mechanism is unknown. It has been shown that protein kinase C (PKC) β2 is over‐expressed in failing human hearts (Circulation 1999;99:384‐91) and that RSG‐induced weight gain is attributable to increased activation of PKCβ in adipose tissue (FASEB J 2006;20:1203‐5). Further, left ventricular mass is reported to be a predictor of heart failure (Eur Heart J 2008;29:741‐747). We, therefore, hypothesized that RSG may induce PKCβ2 over‐expression and increase ventricular mass of the hearts from db/db (D) mice, a mongenic model of obesity and features of type 2 diabetes. Diabetic mice were either untreated (D), treated with RSG (D+RSG) at 26 mg/kg/day or with RSG plus N‐acetylcysteine (NAC, 1.4 g/kg/day) (D+RN), for 3 weeks; NAC can inhibit PKCβ via mechanisms independent of its antioxidant property. Both RSG or RSG+NAC reduced body weight (BW) relative to D group. However, RSG increased ventricular mass and heart weight/BW ratio, accompanied by 1.5‐fold increase of myocardial PKCβ2 protein expression and activation as well as increased protein kinase B/AKT phosphorylation at serine‐473 relative to D (all P<0.05). NAC prevented all these changes. RGS may have increased ventricular mass by inducing PKCβ2 over‐expression. Supported by a CIHR grant (DLS) and an AHFMR postdoctoral fellowship (ZX)