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Los microARN 103 y 107 regulan la sensibilidad a la insulina.

Mirko Trajkovski1, Jean Hausser, Jürgen Soutschek

  • 1Institute for Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli Strasse 16, CH-8093 Zurich, Switzerland.

Nature
|June 10, 2011
PubMed
Resumen

Los microARN 103/107 (miR-103/107) empeoran la homeostasis de la glucosa y la sensibilidad a la insulina. El silenciamiento de estos microARN mejora la sensibilidad a la insulina, identificándolos como un objetivo terapéutico potencial para la diabetes tipo 2.

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Área de la Ciencia:

  • Investigación Metabólica de Investigación.
  • Biología Molecular Biología Molecular
  • Endocrinología Endocrinología.

Sus antecedentes:

  • Los defectos en la señalización de la insulina son clave en el desarrollo de la diabetes tipo 2.
  • Los microARN regulan las funciones biológicas, incluido el metabolismo, pero su papel en la sensibilidad a la insulina in vivo no está claro.

Objetivo del estudio:

  • Para investigar el papel directo de los microARN en la sensibilidad a la insulina in vivo.
  • Para identificar microARN específicos y sus objetivos involucrados en la regulación metabólica.

Principales métodos:

  • Estudió la expresión de microARN en ratones obesos.
  • Niveles manipulados de miR-103/107 (silenciamiento y ganancia de función) in vivo y en adipocitos.
  • Caveolina-1 identificada y validada como gen objetivo directo.
  • Se evaluó la homeostasis de la glucosa, la sensibilidad a la insulina, la señalización de los receptores de insulina y las características de los adipocitos.

Principales resultados:

  • La expresión de miR-103/107 está regulada al alza en ratones obesos.
  • El silenciamiento de miR-103/107 mejora la homeostasis de la glucosa y la sensibilidad a la insulina.
  • La sobreexpresión de miR-103/107 perjudica la homeostasis de la glucosa.
  • Caveolin-1 es un objetivo directo de miR-103/107; su regulación al alza tras la inactivación de miR-103/107 mejora la señalización de los receptores de insulina y la absorción de glucosa.

Conclusiones:

  • miR-103/107 desempeñan un papel crítico en la regulación de la sensibilidad a la insulina.
  • La orientación miR-103/107 ofrece una estrategia terapéutica potencial para la diabetes tipo 2 y la obesidad.