Restoration of Cardiomyocyte Function in Streptozotocin-Induced Diabetic Rats after Treatment with Vanadate in a Tea Decoction

Tod      A. Clark; Thane      G. Maddaford; Paramjit      S. Tappia; Clayton      E. Heyliger; Pallab      K. Ganguly; Grant      N. Pierce

doi:10.2174/138920110793261999

Abstract

Diabetes mellitus is associated with abnormal cardiomyocyte Ca2+ transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP3/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP3/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca2+ transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP3/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function.

Keywords: Cardiomyocyte, calcium, contraction, diabetes, phosphatidic acid, therapy, vanadate, Diabetes mellitus, cardiomyocyte Ca2+, trisphosphate/phospholipase C, streptozotocin, Ca2+ transients, tea, phospholipase D (PLD), diaclygylcerol (DAG), phospholipase C (PLC), inositol 1,4,5 trisphosphate (IP3), insulin-treated diabetics (ID), sodium orthovanadate, normoglycemic, phosphatidic acid (PA), sarcoplasmic reticular Ca2+