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Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Un interruptor inducible en ayunas modula la gluconeogénesis a través del intercambio de activador/coactivador
Yi Liu1, Renaud Dentin, Danica Chen
1The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, California 92037, USA.
Nature
|October 14, 2008
Resumen
El ayuno regula el equilibrio energético cambiando entre CRTC2 y FOXO1. La sirtuina 1 (SIRT1) desacetila el CRTC2, promoviendo la actividad de FOXO1 y manteniendo la homeostasis de la glucosa durante el ayuno prolongado.
Área de la Ciencia:
- Regulación del metabolismo.
- La endocrinología molecular.
- La detección de nutrientes es muy sencilla.
Sus antecedentes:
- El ayuno desencadena la gluconeogénesis hepática a través del glucagón, con la participación de CRTC2 y FOXO1.1.
- La señalización de la insulina disminuye, aumentando la gluconeogénesis durante el ayuno.
- Los cuerpos cetónicos proporcionan combustible compensatorio durante la fase tardía del ayuno.
Objetivo del estudio:
- Investigar el papel de p300 y SIRT1 en el mantenimiento del equilibrio energético durante el ayuno.
- Aclarar la inducción y regulación secuenciales de CRTC2 y FOXO1.
Principales métodos:
- Se utilizaron modelos de ratón con knockout del gen Sirt1 específico del hígado.
- Antagonistas y agonistas SIRT1 administrados.
- Se evaluó la desfosforilación, la acetilación y la ubiquitinación de proteínas.
- Se midió la expresión génica gluconeogénica y la producción de glucosa.
Principales resultados:
- El ayuno induce un interruptor que involucra a p300 y SIRT1 para regular CRTC2 y FOXO1.
- p300 acetila y activa el CRTC2; SIRT1 desacetila y regula a la baja el CRTC2.
- La activación de SIRT1 activa recíprocamente FOXO1 y PGC-1alpha.
- La interrupción de la SIRT1 aumenta la actividad del CRTC2 y la producción de glucosa.
Conclusiones:
- Un interruptor inducible en ayunas de p300 y SIRT1 mantiene el equilibrio energético.
- La activación secuencial de CRTC2 y FOXO1 por este interruptor es crucial para la homeostasis de la glucosa.
- SIRT1 juega un papel clave en la regulación de la gluconeogénesis durante el ayuno.
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