Does the insulin-mimetic action of vanadate involve insulin receptor kinase?
Effects of vanadate administration on the insulin receptor status in liver were examined in streptozotocin-induced diabetic rats. Diabetic rats were characterized by hyperglycemia (4-fold increase), hypoinsulinemia (81% decrease) and a significant (P < 0.01) increase in hepatic insulin receptor numbers. Autophosphorylation of the beta subunit of insulin receptor and its tyrosine kinase activity towards the synthetic peptide (poly glut4tyr1) decreased by approximately 60% as a result of diabetes. After chronic treatment of these rats with sodium orthovanadate, the plasma glucose levels were normalized to near control values with the hypoinsulinemia remaining unaltered. The insulin-stimulated phosphorylation of the beta subunit increased significantly (P < 0.001) in diabetic rats after treatment with vanadate. However, the improvement in the tyrosine kinase activity was marginal. In vitro, vanadate prevented the dephosphorylation of the phosphorylated insulin receptor and increased its tyrosine kinase activity in the absence as well as presence of insulin. The findings of this study further support the view that insulin receptor is one of the sites involved in the insulin-mimetic actions of vanadate.
Pugazhenthi
S
S
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Khandelwal
R L
RL
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D019000:Phosphotyrosine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*; D012016:Reference Values; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D014638:Vanadates / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; D011972:Receptor, Insulin