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 ki nase activity induced by high glucose (HG) in Rat 1 fibroblasts that e xpressed 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 maj or non-transmembrane PTPase in the cytosolic fraction,was increased in NG cells according to Western blots. These results indicate that dese nsitization of insulin receptor function by a high glucose condition i s associated with the activation of PTPase activity. (C) 1994 Academic Press, Inc.