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.