title: Postreceptor defect in insulin action in streptozotocin-induced diabetic rats.
abstract: To clarify the mechanism(s) responsible for the insulin resistance in streptozotocin (STZ)-treated diabetic rats, we studied insulin-induced glucose disposal by using the glucose clamp technique and measured insulin receptor and glucose transporter of muscles. The insulin dose-response curve of the metabolic clearance rate (MCR) of glucose revealed a decrease of the maximal response without a rightward shift in STZ rats. Maximal MCR was even lower when clamped at 300 rather than 150 mg/dl of blood glucose levels. Insulin binding to the crude plasma membrane of muscles from STZ rats was increased compared with controls. The number of glucose transporter of the plasma and microsomal membranes were significantly decreased in STZ rats. These in vivo and in vitro studies using skeletal muscles suggest that in STZ-treated diabetic rats 1) a defect or defects exist in the signal transduction mechanism of insulin in postbinding steps, 2) the decreased maximal MCR is related at least partly to the decrease of glucose transporter numbers, and 3) a defect in glucose metabolism (postglucose transport defect) is also present.
authors.affiliation: Department of Medicine, Kyoto University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Kuzuya
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: A
authors.initials: A
authors.lastname: Kosaki
authors.forename: T
authors.initials: T
authors.lastname: Kakehi
authors.forename: G
authors.initials: G
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Kono
authors.forename: H
authors.initials: H
authors.lastname: Imura
mesh_terms: D000818:Animals; D003571:Cytochalasin B / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: D007328:Insulin; D009004:Monosaccharide Transport Proteins; D003571:Cytochalasin B; D011972:Receptor, Insulin; D005947:Glucose