title: Sodium tungstate administration ameliorated diabetes-induced electrical and contractile remodeling of rat heart without normalization of hyperglycemia.
abstract: Recently, sodium tungstate was suggested to improve cardiac performance of diabetic rats in perfused hearts based on its insulinomimetic activity. In this study, we aimed to investigate the cellular and molecular mechanisms underlying this beneficial effect of sodium tungstate. Tungstate was administered (100 mg/kg/day) to diabetic and control rats intragastrically for 6 weeks. Blood glucose levels increased, whereas body weight, heart weight and plasma insulin levels decreased significantly in diabetic animals. Interestingly, none of these parameters was changed by tungstate treatment. On the other hand, fractional shortening and accompanying intracellular Ca(2+) [Ca(2+)](i) transients of isolated ventricular myocytes were measured, and sodium tungstate was found to improve the peak shortening and the amplitude of [Ca(2+)](i) transients in diabetic cardiomyocytes. Potassium and L-type Ca(2+) currents were also recorded in isolated ventricular cells. Significant restoration of suppressed I (to) and I (ss) was achieved by tungstate administration. Nevertheless, L-type calcium currents did not change either in untreated or treated diabetic rats. Tissue biochemical parameters including TBARS, protein carbonyl content, xanthine oxidase (XO) and xanthine dehydogenase (XDH) were also determined, and diabetes revealed a marked increase in TBARS and carbonyl content which were decreased significantly by tungstate treatment. Conversely, although XO and XDH activities didn't change in untreated diabetic rats, a remarkable but insignificant decrease was detected in treated animals. In conclusion, tungstate treatment improved diabetes-induced contractile abnormalities via restoration of dysregulated [Ca(2+)](i) and altered ionic currents. This beneficial effect is due to antioxidant property of sodium tungstate rather than normalization of hyperglycemia.
authors.affiliation: Faculty of Medicine, Department of Biophysics, Akdeniz University, Antalya, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Aydemir
authors.forename: Nihal
authors.initials: N
authors.lastname: Ozturk
authors.forename: Serdar
authors.initials: S
authors.lastname: Dogan
authors.forename: Mutay
authors.initials: M
authors.lastname: Aslan
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Olgar
authors.forename: Semir
authors.initials: S
authors.lastname: Ozdemir
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D055724:Electrophysiological Phenomena; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006943:Hyperglycemia / Q000473:pathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress; D018408:Patch-Clamp Techniques; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D017973:Tungsten Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D017392:Thiobarbituric Acid Reactive Substances; D017973:Tungsten Compounds; C025399:sodium tungstate(VI); D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D002118:Calcium