Hypoglycemic Effects Of Bis (α-furancarboxylato) Oxovanadium (IV) In Alloxan-diabetic Mice And Its Preliminary Mechanisms

AIM Bis(α-furancarboxylato)oxovanadium(IV)(VO-FA), a new orally active antidiabetic vanadyl complex has been synthesized and characterized. The present study was carried out to evaluate the hypoglycemic effects of VO-FA in alloxan-diabetic mice and its preliminary mechanisms.Methods Diabetic mice were induced by injecting 60 mg.kg^-1 alloxan through caudal vein. Blood glucose level, water and food consumption were measured after administration of VO-FA intragastrically to alloxan-diabetic mice and normal mice for 14 days. Glucose uptake and lipogenesis in isolated rat adipocytes were determined using 2-deoxy-D-[³H]-glucose and D-[³H]-glucose, respectively. Lipolysis was assayed by free fat acid (FFA) released from isolated rat adipocytes treated with epinephrine. Results Administration of VO-FA (28.9 mg.kg^-1.d, 59.8 mg.kg^-1.d) can significantly decrease blood glucose levels, food and water intake in alloxan-diabetic mice, but not in normal mice. In vitro, VO-FA concentration-dependently significantly increase the uptake of 2-deoxy-D-[³H]-glucose and the transformation from D-[³H]-glucose to lipid in isolated rat adipocytes at concentrations of 0.1-2 mM, with EC50 values of 0.31 ± 0.08 mM and 0.49 ±0.12 mM, respectively. The actions of VO-FA in uptake and transformation of glucose were enhanced in the presence of insulin (200 nM). Furthermore, VO-FA, like insulin, markedly inhibited FFA release from isolated rat adipocytes treated with epinephrine, and the IC50 value was 1.20 ± 0.23 mM.Conclusion VO-FA had a hypoglycemic effect in alloxan-diabetic mice. Its mechanisms were related to enhancing glucose uptake and lipogenesis, inhibiting lipolysis, but not to directly stimulating the synthesis and secretion of insulin.