Vanadium increases GLUT4 in diabetic rat skeletal muscle.
The effect of vanadium in lowering blood glucose in diabetic animals is well established; however, the exact mechanism of action of vanadium still eludes us. There are several reports from in vitro studies indicating that vanadium increases enzyme activity in insulin signalling pathways; however, these findings have not been duplicated in vivo. Glucose transporters (GLUT) have a major role to play in any glucoregulatory effects. Insulin dependent GLUT4 is a major glucose transporter present in skeletal muscle, adipocytes and heart. In the present study we found that the plasma glucose in streptozotocin (STZ) diabetic animals was restored to normal following treatment with a single dose of BMOV, an organic vanadium compound, given by oral gavage (0.6 mmol/kg), similar to the response with chronic BMOV treatment. The response to BMOV by oral gavage was rapid and the animals were normoglycemic within 24 h of treatment and still demonstrated a significant effect even after 72 h. Using a specific antibody against GLUT4 we found an overall reduction in the GLUT4 in the total membrane fraction in skeletal muscle of diabetic animals. However, with a single dose of BMOV the GLUT4 level was restored to normal. This is the first report that establishes a direct effect of vanadium on the regulation of GLUT4 expression in diabetic animals in vivo, and may at least partially explain the glucoregulatory effects of vanadium.
Mohammad
Askar
A
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Sharma
Vijay
V
McNeill
John H
JH
D000818:Animals; D017931:DNA Primers / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation; D014638:Vanadates / Q000494:pharmacology*
D017931:DNA Primers; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011753:Pyrones; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates