Olichon-Berthe C, Hauguel-De Mouzon S, Péraldi P, Van Obberghen E, Le Marchand-Brustel Y
INSERM U145, Faculté de Médecine, Nice, France.
Diabetologia. 1994 Jan;37(1):56-60. doi: 10.1007/BF00428778.
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.
为研究磷酸酪氨酸磷酸酶在胰岛素抵抗中可能的作用，我们检测了正常小鼠、经金硫葡萄糖处理的胰岛素抵抗肥胖小鼠的胞质和膜制剂使胰岛素受体去磷酸化的能力。制剂取自肝脏、心脏、膈肌和后肢肌肉，以磷酸化胰岛素受体为底物，采用免疫酶法测定其磷酸酪氨酸磷酸酶活性。肝脏胞质和微粒体磷酸酪氨酸磷酸酶比其他组织的制剂活性更强，且能够以剂量和时间依赖的方式使胰岛素受体几乎完全去磷酸化。与正常小鼠相比，肥胖小鼠肝脏、膈肌和心脏的胞质及膜相关磷酸酪氨酸磷酸酶未发生变化。相反，肥胖小鼠后肢肌肉的胞质磷酸酪氨酸磷酸酶活性降低，但膜相关磷酸酪氨酸磷酸酶活性未降低。这些结果表明，磷酸酪氨酸磷酸酶的调节具有组织特异性。此外，虽然不能排除特定变化，但总磷酸酪氨酸磷酸酶活性的改变似乎在肥胖小鼠所有组织的胰岛素抵抗中不起重要作用。
