Effect of vanadium(IV) compounds in the treatment of diabetes: in vivo and in vitro studies with vanadyl sulfate and bis(maltolato)oxovandium(IV).
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.
Willsky
G R
GR
Toxicology Research Center, SUNY at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY 14214, USA. gwillsky@acsu.buffalo.edu
Goldfine
A B
AB
Kostyniak
P J
PJ
McNeill
J H
JH
Yang
L Q
LQ
Khan
H R
HR
Crans
D C
DC
D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004578:Electron Spin Resonance Spectroscopy; D005215:Fasting; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008297:Male; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013311:Streptozocin; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism; D016896:Treatment Outcome; D014638:Vanadates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014639:Vanadium / Q000097:blood / Q000652:urine; D017968:Vanadium Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D001059:Apoproteins; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D011753:Pyrones; D012709:Serum Albumin; D014168:Transferrin; D017968:Vanadium Compounds; C028284:apotransferrin; D014639:Vanadium; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D013311:Streptozocin; C034028:vanadyl sulfate