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Báo cáo Y học: Coordinated action of protein tyrosine phosphatases in insulin signal transduction

Insulin is the principal regulatory hormone involved in the tight regulation of fuel metabolism. In response to blood glucose levels, it is secreted by the b cells of the pancreas and exerts its effects by binding to cell surface receptors that are present on virtually all cell types and tissues. In humans, perturbations in insulin function and/or secretion lead to diabetes mellitus, a severe disorder primarily characterized by an inability to maintain blood glucose homeostasis. Furthermore, it is estimated that 90–95% of diabetic patients exhibit resistance to insulin action | Eur. J. Biochem. 269 1050-1059 2002 FEBS 2002 MINIREVIEW Coordinated action of protein tyrosine phosphatases in insulin signal transduction Alan Cheng Nadia Dube Feng Gu and Michel L. Tremblay Department of Biochemistry and McGill Cancer Center McGill University Montreal Quebec Canada Insulin is the principal regulatory hormone involved in the tight regulation of fuel metabolism. In response to blood glucose levels it is secreted by the b cells of the pancreas and exerts its effects by binding to cell surface receptors that are present on virtually all cell types and tissues. In humans perturbations in insulin function and or secretion lead to diabetes mellitus a severe disorder primarily characterized by an inability to maintain blood glucose homeostasis. Furthermore it is estimated that 90-95 of diabetic patients exhibit resistance to insulin action. Thus an understanding of insulin signal transduction and insulin resistance at the molecular level is crucial to the understanding of the pathogenesis of this disease. The insulin receptor IR is a transmembrane tyrosine kinase that becomes activated upon ligand binding. Consequently the receptor and its down stream substrates become tyrosine phosphorylated. This activates a series of intracellular signaling cascades which coordinately initiate the appropriate biological response. One important mechanism by which insulin signaling is regulated involves the protein tyrosine phosphatases PTPs which may either act on the IR itself and or its substrates. Two well characterized examples include leuckocyte antigen related LAR and protein tyrosine phosphatase-lB PTP-1B . The present review will discuss the current knowledge of these two and other potential PTPs involved in the insulin signaling pathway. Keywords diabetes insulin receptor protein tyrosine phosphatase knockout mice signaling. INTRODUCTION Insulin is the most potent anabolic hormone identified to date. It is produced and secreted in a regulated fashion by the b