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.