Effect of in vivo vanadate treatment on insulin receptor tyrosine kinase activity in partially pancreatectomized diabetic rats.
Liver-purified insulin receptor tyrosine kinase (IRTK) activity was examined in partially pancreatectomized rats following normalization of blood glucose concentration by either phlorizin or vanadate treatment. Chronic moderate hyperglycemia did not modify the IRTK activity, despite the presence of in vivo and in vitro insulin resistance. Oral vanadate administration for 3 weeks normalized glucose tolerance and caused a 2.5-fold increase in basal IRTK activity. In contrast, correction of hyperglycemia with phlorizin, an inhibitor of renal glucose reabsorption, did not change the IRTK activity, although glucose tolerance was returned to normal. The vanadate-induced effect on basal IRTK was due to an increase in Vmax of the enzyme; the Km remained unchanged. The insulin-stimulated IRTK activity was not affected by either vanadate or phlorizin treatment. These results suggest that: 1) partial (90%) pancreatectomy in rats causes insulin resistance in the absence of in vitro alterations in IRTK and 2) correction of chronic hyperglycemia with vanadate, but not with phlorizin, is associated with an increased basal activation of the protein tyrosine kinase in liver insulin receptors.
Cordera
R
R
Department of Medicine, University of Genova, Italy.
Andraghetti
G
G
DeFronzo
R A
RA
Rossetti
L
L
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010180:Pancreatectomy / Q000379:methods; D010695:Phlorhizin / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology*
D007328:Insulin; D014638:Vanadates; D010695:Phlorhizin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D010744:Phosphoric Monoester Hydrolases