Effect of vanadium(IV) compounds in the treatment of diabetes: in vivo andin vitro studies with vanadyl sulfate and bis(maltolato)oxovandium(IV)

Vanadyl sulfate (VOSO4) was given orally to 16 subjects with type 2 diabete s mellitus for 6 weeks at a dose of 25, 50, or 100 mg vanadium (V) daily [G oldfine et al., Metabolism 49 (2000) 1-12]. Elemental V was determined by g raphite furnace atomic absorption spectrometry (GFAAS). There was no correl ation of V in serum with clinical response, determined by reduction of mean fasting blood glucose or increased insulin sensitivity during euglycemic c lamp. To investigate the effect of administering a coordinated V, plasma gl ucose levels were determined in streptozotocin (STZ)-induced diabetic rats treated with the salt (VOSO4) or the coordinated V compound bis(maltolato)o xovandium(IV) (abbreviated as VO(malto)(2)) administered by intraperitoneal (i.p.) injection. There was no relationship of blood V concentration with plasma glucose levels in the animals treated with VOSO4, similar to our hum an diabetic patients. However, with VO(malto)(2) treatment, animals with lo w plasma glucose tended to have high blood V. To determine if V binding to serum proteins could diminish biologically active serum V, binding of both VOSO4 and VO(malto)(2) to human serum albumin (HSA), human apoTransferrin ( apoHTf) and pig immunoglobulin (IgG) was studied with EPR spectroscopy. Bot h VOSO4 and VO(malto)(2) bound to HSA and apoHTf forming different V-protei n complexes, while neither V compound bound to the IgG. VOSO4 and VO(malto) (2) showed differences when levels of plasma glucose and blood V in diabeti c rodents were compared, and in the formation of V-protein complexes with a bundant serum proteins. These data suggest that binding of V compounds to l igands in blood, such as proteins, may affect the available pool of V for b iological effects. (C) 2001 Elsevier Science B.V. All rights reserved.