Dephosphorylation of the insulin receptor partially restores the decreased autophosphorylation in streptozotocin induced diabetic rats.
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)
Iwama
N
N
First Department of Medicine, Osaka University Medical School, Japan.
Watarai
T
T
Kajimoto
Y
Y
Yamasaki
Y
Y
Yokoyama
T
T
Kawamori
R
R
Kamada
T
T
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
D007328:Insulin; C008147:insulin, iodo-; D011494:Protein Kinases; D011972:Receptor, Insulin; D000469:Alkaline Phosphatase