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

• Published in: Journal of inorganic biochemistry Vol. 85; no. 1; pp. 33 - 42
• Main Authors: Willsky, G.R, Goldfine, A.B, Kostyniak, P.J, McNeill, J.H, Yang, L.Q, Khan, H.R, Crans, D.C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2001
• Subjects: Animals; Apoproteins - chemistry; Apoproteins - metabolism; Biological Availability; Bis(maltolato)oxovandium(IV); Blood Glucose - analysis; Blood Glucose - metabolism; BMOV; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Electron Spin Resonance Spectroscopy; EPR; Fasting; Humans; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - metabolism; Hypoglycemic Agents - pharmacology; Immunoglobulin G - chemistry; Immunoglobulin G - metabolism; Male; Pyrones - chemistry; Pyrones - metabolism; Pyrones - pharmacology; Rats; Rats, Wistar; Serum Albumin - chemistry; Serum Albumin - metabolism; Streptozocin; Transferrin - chemistry; Transferrin - metabolism; Treatment Outcome; Vanadates - chemistry; Vanadates - metabolism; Vanadates - pharmacology; Vanadium - blood; Vanadium - urine; Vanadium Compounds - chemistry; Vanadium Compounds - metabolism; Vanadium Compounds - pharmacology; Vanadyl sulfate; EPR; EPR, electron paramagnetic resonance; GFAAS, graphite furnace atomic absorption spectrometry; V, vanadium; STZ, streptozotocin; IgG, immunoglobulin (purified IgG fraction); BMOV; HSA, human serum albumin; Vanadyl sulfate; VOSO 4, vanadyl sulfate; i.p., intraperitoneal; VO(malto) 2 frequently seen as BMOV, bis(maltolato)oxovandium(IV); NMR, nuclear magnetic resonance; Diabetes; apoHTf, human apotransferrin; Hepes, N-[2[hydroxyethyl]piperazine- N′-[2-ethanesulfonic acid]; Bis(maltolato)oxovandium(IV)
• DOI: 10.1016/S0162-0134(00)00226-9
• ISSN: 0162-0134

Vanadyl sulfate (VOSO 4) was given orally to 16 subjects with type 2 diabetes mellitus for 6 weeks at a dose of 25, 50, or 100 mg vanadium (V) daily [Goldfine et al., Metabolism 49 (2000) 1–12]. Elemental V was determined by graphite furnace atomic absorption spectrometry (GFAAS). There was no correlation of V in serum with clinical response, determined by reduction of mean fasting blood glucose or increased insulin sensitivity during euglycemic clamp. To investigate the effect of administering a coordinated V, plasma glucose levels were determined in streptozotocin (STZ)-induced diabetic rats treated with the salt (VOSO 4) or the coordinated V compound bis(maltolato)oxovandium(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 VOSO 4, similar to our human diabetic patients. However, with VO(malto) 2 treatment, animals with low 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 VOSO 4 and VO(malto) 2 to human serum albumin (HSA), human apoTransferrin (apoHTf) and pig immunoglobulin (IgG) was studied with EPR spectroscopy. Both VOSO 4 and VO(malto) 2 bound to HSA and apoHTf forming different V-protein complexes, while neither V compound bound to the IgG. VOSO 4 and VO(malto) 2 showed differences when levels of plasma glucose and blood V in diabetic rodents were compared, and in the formation of V-protein complexes with abundant serum proteins. These data suggest that binding of V compounds to ligands in blood, such as proteins, may affect the available pool of V for biological effects.