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Insulin receptor dephosphorylation by phosphotyrosine phosphatases obtained from insulin-resistant obese mice
C Olichon-Berthe1, S Hauguel-De Mouzon, P Péraldi
1INSERM U145, Faculté de Médecine, Nice, France.
Abstract:
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.
Insights
Phosphotyrosine phosphatases dephosphorylate insulin receptors. Activity changes in obese mice are tissue-specific, with decreased cytosolic activity in hindleg muscle, suggesting a limited role in overall insulin resistance.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Insulin resistance is a complex metabolic disorder.
- Phosphotyrosine phosphatases (PTPs) play a role in signal transduction pathways.
- The specific involvement of PTPs in insulin resistance requires further investigation.
Purpose of the Study:
- To investigate the role of phosphotyrosine phosphatases in insulin resistance.
- To examine PTP activity in dephosphorylating insulin receptors in various tissues of lean and obese mice.
- To determine tissue-specific alterations in PTP activity associated with obesity and insulin resistance.
Main Methods:
- Prepared cytosolic and membrane fractions from liver, heart, diaphragm, and hindleg muscle of lean and obese mice.
- Measured phosphotyrosine phosphatase activity using an immunoenzymatic assay with phosphorylated insulin receptors as substrate.
- Compared PTP activity between lean and insulin-resistant/obese mouse models.
Main Results:
- Liver cytosolic and particulate PTPs demonstrated potent insulin receptor dephosphorylation in a dose- and time-dependent manner.
- No significant changes in PTP activity were observed in the liver, diaphragm, and heart of obese mice compared to lean controls.
- A decrease in cytosolic PTP activity, but not membrane-associated activity, was noted in the hindleg muscles of obese mice.
Conclusions:
- Phosphotyrosine phosphatase regulation is tissue-specific.
- Altered total PTP activity does not appear to be a primary driver of insulin resistance across all tissues in obese mice.
- Specific PTP alterations in certain tissues, like hindleg muscle, may still contribute to insulin resistance, warranting further study.