Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats

Simple Summary Diabetes mellitus is a disease that affects some metabolic processes, altering the metabolism of trace elements associated with the antioxidant defense system. The insulin-mimetic activity of vanadium has received attention in recent years. However, the use of vanadium as an antidiabetic agent is limited due to its pro-oxidant properties, which are probably caused by interactions with other trace elements. There is currently little information on the interactions between vanadium and zinc, copper and manganese in diabetic rats. For these reasons, the objective of this study was to examine whether diabetic rats treated with bis(maltolato)oxovanadium(IV) (BMOV(IV)) undergo alterations in zinc, copper and manganese homeostasis, and whether such changes are related to the gene expression of the divalent metal transporter 1 (DMT1). The results obtained from this study showed that the metabolism of Zn, Cu and, to a lesser extent, Mn is altered by diabetes and that BMOV(IV) administered to diabetic rats at a dose of 3 mg V/day reverted the alterations in zinc and copper homeostasis produced by diabetes. The effect of this supplementation was possibly mediated by a decrease in food intake and DMT1 gene expression. Our aim was to examine whether vanadium (IV) corrects alterations in zinc, copper and manganese homeostasis, observed in streptozotocin-induced hyperglycemic rats, and whether such changes are related to divalent metal transporter 1 (DMT1) mRNA expression, and antioxidant and proinflammatory parameters. Four groups of Wistar rats were examined: control; hyperglycemic (H); hyperglycemic treated with 1 mg V/day (HV); and hyperglycemic treated with 3 mg V/day (HVH). Vanadium was supplied in drinking water as bis(maltolato)oxovanadium(IV) for five weeks. Zinc, copper and manganese were measured in food, excreta, serum and tissues. DMT1 mRNA expression was quantified in the liver. Hyperglycemic rats showed increased Zn and Cu absorption and content in the liver, serum, kidneys and femurs; DMT1 expression also increased (p < 0.05 in all cases). HV rats showed no changes compared to H rats other than decreased DMT1 expression (p < 0.05). In the HVH group, decreased absorption and tissular content of studied elements (p < 0.05 in all cases) and DMT1 expression compared to H (p < 0.05) were observed. Liver zinc, copper and manganese content correlated positively with glutathione peroxidase activity and negatively with catalase activity (p < 0.05 in both cases). In conclusion, treatment with 3 mg V/d reverted the alterations in zinc and copper homeostasis caused by hyperglycemia, possibly facilitated by decreased DMT1 expression.

Automated summary

The study found that diabetes alters the metabolism of zinc, copper, and manganese, and treatment with vanadium(IV) can reverse the changes in zinc and copper homeostasis caused by hyperglycemia. This effect is possibly mediated by a decrease in DMT1 gene expression.