INSULIN-RECEPTOR DEPHOSPHORYLATION BY PHOSPHOTYROSINE PHOSPHATASES OBTAINED FROM INSULIN-RESISTANT OBESE MICE

To study the possible involvement of phosphotyrosine phosphatases in i nsulin resistance, the ability of cytosolic and membrane preparations to dephosphorylate insulin receptors was examined in lean and goldthio glucose-treated insulin-resistant and obese mice. Preparations were ob tained from liver, heart, diaphragm and hindleg muscle and their phosp hotyrosine phosphatase activities were measured using an immunoenzymat ic assay with phosphorylated insulin receptors as substrate. Liver cyt osolic and particulate phosphotyrosine phosphatases were more potent t han preparations from other tissues and were able to almost completely dephosphorylate the insulin receptor in a dose- and time-dependent ma nner. No change was observed in cytosolic and membrane-associated phos photyrosine phosphatases in liver, diaphragm, and heart of obese mice compared with lean mice. In contrast, cytosolic, but not membrane-asso ciated, phosphotyrosine phosphatase activity was decreased in hindleg muscles of obese mice. These results suggest that the regulation of ph osphotyrosine phosphatases is tissue-specific. In addition, alteration s in total phosphotyrosine phosphatase activity do not appear to play an important role in insulin resistance in all tissues of obese mice, although specific changes cannot be excluded.