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2004, Número 3

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Med Sur 2004; 11 (3)


Mecanismos moleculares de resistencia

Zamora-Valdés D, Chávez-Tapia NC, Méndez-Sánchez N

Idioma: Español
Referencias bibliográficas: 94
Paginas: 149-159
Archivo PDF: 100.41 Kb.


RESUMEN

Los mecanismos moleculares de la resistencia a la insulina constituyen una variedad de complejas alteraciones en la señalización de la insulina y en la regulación normal de la expresión y síntesis de adipocinas. Las principales involucradas son TNF-a y los ácidos grasos libres. Hasta el momento, la disminución de la fosforilación tirosina cinasa del receptor y sus sustratos, junto con el aumento de la fosforilación serina cinasa, es el principal candidato iniciador. Esta forma de activación no conduce la señal por la vía de PI3-K, pero produce la activación de fosfatasas de fosfotirosina con retroalimentación negativa sobre el receptor. La cinasa inhibidora del NK-kB es el mediador de TNF-a para esta activación. El NK-kB disminuye la expresión de PPAR-g y adiponectina, con disminución en sus efectos protectores. La leptina posee efectos protectores, sin embargo, se cree que existe una forma de resistencia a sus efectos en la obesidad. Los ácidos grasos libres son probables mediadores sistémicos de la acción de TNF-a porque producen resistencia hepática a la insulina y alteraciones en el metabolismo de los lípidos e hidratos de carbono que desembocan en mayor resistencia a la insulina. El objetivo de esta revisión es presentar los resultados de estudios experimentales in vitro e in vivo y de estudios clínicos relacionados a la resistencia a la insulina en la obesidad, para ilustrar el estado actual de la investigación a nivel molecular.


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