2004, Number 3
Zamora-Valdés D, Chávez-Tapia NC, Méndez-Sánchez N
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ABSTRACTThe molecular mechanisms of insulin resistance consist in a variety of complex disturbances in insulin signaling and in normal expression and regulation of adipokynes. The principal candidates are TNF-a and free fatty acids. At the moment, the downregulation of tirosin kinase activation of insulin receptor and its substrates, along with upregulation of serine kinase activation, is the main potential initiator. This form of activation does not conduce the signal of insulin through PI3-K, but is able of activating phosphotirosine phosphatases with negative feedback over the receptor. The inhibitory NK-kB kinase is probably the mediator of this activation. NK-kB produces downregulation of PPAR-g and adiponectin, with the lost of its potential benefical effects. Leptin has also protective effects, however, it has been suggested that there is also a leptin resistance. Free fatty acids are probably systemic mediators of TNF-a insulin resistance as they produce hepatic insulin resistance and disturbances in lipid and carbohydrates metabolism which cause more insulin resistance. The goal of this review is to present the results of in vitro and in vivo experimental and clinical studies related to insulin resistance in obesity, to ilustrate the state of the art of molecular research in the field.