Effects of vanadium complexes with organic ligands on glucose metabolism: a comparison study in diabetic rats

1 Vanadium compounds can mimic actions of insulin through alternative signa lling pathways. The effects of three organic vanadium compounds were studie d in non-ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VA c), vanadyl 3-ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM ). A simple inorganic vanadium salt, vanadyl sulphate (VS) was also studied . 2 Oral administration of the three organic vanadium compounds (125 mg vanad ium element l(-1) in drinking fluids) for up to 3 months induced a faster a nd larger fall in glycemia (VAc being the most potent) than VS. Glucosuria and tolerance to a glucose load were improved accordingly. 3 Activities and mRNA levels of key glycolytic enzymes (glucokinase and L-t ype pyruvate kinase) which are suppressed in the diabetic liver, were resto red by vanadium treatment. The organic forms showed greater efficacy than V S, especially VAc. 4 VAc rats exhibited the highest levels of plasma or tissue vanadium, most likely due to a greater intestinal absorption. However, VAc retained its po tency when given as a single i.p. injection to diabetic rats. Moreover, the re was no relationship between plasma or tissue vanadium levels and any par ameters of glucose homeostasis and hepatic glucose metabolism. Thus, these data suggest that differences in potency between compounds are due to diffe rences in their insulin-like properties. 5 There was no marked toxicity observed on hepatic or renal function. Howev er, diarrhoea occurred in 50% of rats chronically treated with VS, but not in those receiving the organic compounds. 6 In conclusion, organic vanadium compounds, in particular VAc, correct the hyperglycemia and impaired hepatic glycolysis of diabetic rats more safely and potently than VS. This is not simply due to improved intestinal absorp tion, indicating more potent insulin-like properties.