Insulin receptor tyrosine kinase is defective in skeletal muscle of insulin-resistant obese mice


Obese syndromes of genetic origin or experimentally induced are characterized by resistance to insulin both in vivo (association of hyperglycaemia and hyperinsulinaemia) and in vitro1. Thus, skeletal muscle of obese mice, which is the most important target organ for the action of insulin, displays a reduced response to insulin2–4. This hormonal resistance cannot be explained by the moderate decrease in the number of insulin receptors found in obese animals3–5. In fact, it is generally believed that a biochemical event occurring very early after binding of insulin to its receptor, which is the first step in insulin action, is defective in obesity. One of the earliest post-binding events so far recognized, and which is thought to have a key role in cellular signalling by the insulin receptor, is the insulin-stimulated phosphorylation of its receptor6–8. In an effort to localize the defect responsible for the insulin resistance in obesity, we have studied the insulin receptor protein kinase activity and we show here that insulin receptors from skeletal muscles of insulin-resistant obese mice have an altered kinase activity for phosphorylation of both the receptor itself and of exogeneous substrates.

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Le Marchand-Brustel, Y., Grémeaux, T., Ballotti, R. et al. Insulin receptor tyrosine kinase is defective in skeletal muscle of insulin-resistant obese mice. Nature 315, 676–679 (1985).

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