Mechanism on insulin-like action of vanadyl sulfate: studies on interaction between rat adipocytes and vanadium compounds.
When rats with streptozotocin (STZ)-induced diabetes were given a daily intraperitoneal (i.p.) injection of VOSO4 (+4 oxidation state of vanadium), their serum glucose dropped from hyperglycemic level to normal level within 2d and serum free fatty acid (FFA) level also dropped to normal level. Vanadium was incorporated in most organs as well as in the adipose tissues, as detected by neutron activation analysis (NAA). The mechanism for the insulin-like action vanadium in terms of FFA release from isolated rat adipocytes was investigated: (1) Vanadyl (IV) and vanadic (III) ions normalize the FFA release in the adipocytes treated with epinephrine; (2) vanadate (V) ion treated with ascorbic acid, cysteine or glucose is effective in normalizing the FFA release but vanadate ion alone has no effect on FFA release; (3) vanadyl ion is incorporated into the adipocytes, while vanadate ion is not, as indicated by ESR spectroscopy; and (4) vanadyl ion can act on the glucose transporter, as indicated by experiments using cytochalasin B which is an inhibitor of this transporter. From these results, the normalization of both serum glucose and FFA levels by vanadyl ion was concluded to be due to the incorporation of vanadyl ion into the adipocytes, in which the metal ion acts on the glucose transporter and induces both the promotion of glucose uptake and the decrease of FFA release form peripheral adipocytes. The vanadyl state was suggested to be a possible pharmacologically active form of vanadium allowing the insulin-like action.(ABSTRACT TRUNCATED AT 250 WORDS)
D017667:Adipocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014018:Tissue Distribution; D017968:Vanadium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D003573:Cytochrome b Group; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D017968:Vanadium Compounds; C034028:vanadyl sulfate; D005947:Glucose