Impaired insulin action but normal insulin receptor activity in diabetic rat liver: effect of vanadate.
In vivo insulin resistance is a characteristic of the liver and peripheral tissues in 10-wk-old female rats with non-insulin-dependent diabetes induced by streptozotocin given on day 5 after birth. Oral administration of vanadate (0.2 mg/ml) for 20 days in the diabetic rats lowered their plasma glucose levels to normal values without affecting their basal plasma insulin levels. In the basal state as well as after submaximal or maximal hyperinsulinemia (euglycemic clamp studies), peripheral glucose utilization and hepatic glucose production in vivo were normalized in the diabetic rats after the vanadate treatment. In wheat germ agglutinin purified receptors, 125I-labeled porcine insulin binding, basal and insulin-stimulated insulin receptor kinase activities for both the autophosphorylation of the beta-subunit and the phosphorylation of the artificial substrate poly (Glu-Tyr) 4:1, were found identical in diabetic and control rats, treated or not with vanadate. Liver phosphoenolpyruvate carboxykinase activity was significantly enhanced in untreated diabetic rats (P less than 0.01) as compared with control rats and returned to normal values after the 20-day vanadate treatment. Thus, in that model of non-insulin-dependent diabetes, 1) oral vanadate exerts a corrective insulin-like effect on impaired insulin action both at the level of liver and peripheral tissues, 2) impaired insulin action with no alteration of the insulin receptor tyrosine kinase is observed in the liver of untreated rats, and 3) corrective effect of vanadate on liver glucose metabolism is probably distal to the insulin receptor kinase activity.
Blondel
O
O
Laboratoire de Physiologie du Développement, Université Paris VII, Centre National de la Recherche Scientifique Unité de Recherche Associée 307, France.
Simon
J
J
Chevalier
B
B
Portha
B
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D014638:Vanadates / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D014638:Vanadates; D011972:Receptor, Insulin; D010729:Phosphoenolpyruvate Carboxykinase (GTP)