Effects of triiodothyronine on PKC-mediated phosphorylation of Cx43 in the diabetic rat heart

Abnormalities in cardiac function have been extensively documented in experimental and clinical diabetes. Subcellular remodeling and defects in intracellular Ca²⁺ signaling can contribute to cardiomyopathy resulting in depression of systolic and diastolic function. Moreover diabetes is associated with activation of PKC(Protein Kinase C) signaling pathway account for reduced myocardial gap junctional intercellular communication. Previously we reported that expression of PKCε was enhanced and PKCε-mediated phosphorylation of Cx43(Connexin43) was augmented in association with cell-to-cell decoupling in diabetic heart. It is documented that the diabetic shows hypothyroidism. Thyroid hormones are playing an important role in maintain of cardiac function. Therefor this study was undertaken to examine whether triiodothyronine(T3) treatment in physiological dosage(0.3μg/100g/day) or pharmacological dosage(10μg/100g/day) during chronic stage of diabetes can influence PKC signaling and affect on Cx43 phosphorylation as well as myocardial intercellular electrical coupling. Triiodothyronine showed an ameliorative effect on PKCε-mediated phosphorylation of Cx43 in association with recovery of electrical cell decoupling in the diabetic rat heart. [Jpn J Physiol 54 Suppl:S100 (2004)]