Insulin receptor dephosphorylation by phosphotyrosine phosphatases obtained from insulin-resistant obese mice.
To study the possible involvement of phosphotyrosine phosphatases in insulin resistance, the ability of cytosolic and membrane preparations to dephosphorylate insulin receptors was examined in lean and goldthioglucose-treated insulin-resistant and obese mice. Preparations were obtained from liver, heart, diaphragm and hindleg muscle and their phosphotyrosine phosphatase activities were measured using an  immunoenzymatic assay with phosphorylated insulin receptors as substrate. Liver cytosolic and particulate phosphotyrosine phosphatases were more potent than preparations from other tissues and were able to almost completely dephosphorylate the insulin receptor in a dose- and time-dependent manner. No change was observed in cytosolic and membrane-associated phosphotyrosine phosphatases in liver, diaphragm, and heart of obese mice compared with lean mice. In contrast, cytosolic, but not membrane-associated, phosphotyrosine phosphatase activity was decreased in hindleg muscles of obese mice. These results suggest that the regulation of phosphotyrosine phosphatases is tissue-specific. In addition, alterations 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.
Olichon-Berthe
C
C
INSERM U145, Faculté de Médecine, Nice, France.
Hauguel-De Mouzon
S
S
Péraldi
P
P
Van Obberghen
E
E
Le Marchand-Brustel
Y
Y
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009765:Obesity / Q000201:enzymology*; D009928:Organ Specificity; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*
D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases