High glucose condition activates protein tyrosine phosphatases and deactivates insulin receptor function in insulin-sensitive rat 1 fibroblasts.
To investigate the mechanism for the impairment of insulin receptor kinase activity induced by high glucose (HG) in Rat 1 fibroblasts that expressed human insulin receptors (HIRc), we measured protein tyrosine phosphatase (PTPase) activity in HG cells. Incubating HIRc cells for 4 days in 27 mM D-glucose (HG) stimulated cytosolic PTPase activities, but not particulate PTPase activity as determined by two methods using the dephosphorylation of insulin receptors. Furthermore, PTP1B, a major non-transmembrane PTPase in the cytosolic fraction, was increased in HG cells according to Western blots. These results indicate that desensitization of insulin receptor function by a high glucose condition is associated with the activation of PTPase activity.
Ide
R
R
Third Department of Medicine, Shiga University of Medical Science, Japan.
Maegawa
H
H
Kikkawa
R
R
Shigeta
Y
Y
Kashiwagi
A
A
D000818:Animals; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D014162:Transfection
D007328:Insulin; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases; D005947:Glucose