title: Dephosphorylation of the insulin receptor partially restores the decreased autophosphorylation in streptozotocin induced diabetic rats.
abstract: The insulin resistance seen in diabetes mellitus has been attributed partly to impaired autophosphorylation of the insulin receptor. It has been suggested that the phosphorylation of serine and/or threonine residues of the insulin receptor may reduce tyrosine autophosphorylation in streptozotocin-induced diabetic rats (STZ-D rats). To elucidate the mechanisms of decreased autophosphorylation of the insulin receptor in diabetic rats, we have investigated the effect of dephosphorylation of the insulin receptor by alkaline phosphatase on the insulin- and protein kinase-stimulating incorporation of 32P into the receptor of the liver from STZ-D rats. Both basal and insulin-stimulated autophosphorylations of the insulin receptor from STZ-D rats were significantly impaired to those from normal rats. Dephosphorylation of the insulin receptor by alkaline phosphatase resulted in an increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats (43 +/- 13% to 66 +/- 14%, P less than 0.05), but not from normal rats (100% to 109 +/- 12%, NS). Although maximal autophosphorylation of the dephosphorylated insulin receptor was still lower in STZ-D rats than in normal rats, the increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats by dephosphorylation was higher than that from normal (159.2 +/- 27.2% vs 108.0 +/- 12.4%, p less than 0.01), supporting the idea that the residues of the insulin receptor of STZ-D rats was highly phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: First Department of Medicine, Osaka University Medical School, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Iwama
authors.forename: T
authors.initials: T
authors.lastname: Watarai
authors.forename: Y
authors.initials: Y
authors.lastname: Kajimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: R
authors.initials: R
authors.lastname: Kawamori
authors.forename: T
authors.initials: T
authors.lastname: Kamada
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*; D012016:Reference Values
chemical_list: D007328:Insulin; C008147:insulin, iodo-; D011494:Protein Kinases; D011972:Receptor, Insulin; D000469:Alkaline Phosphatase