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La ciclina D1-Cdk4 controla el metabolismo de la glucosa independientemente de la progresión del ciclo celular

Yoonjin Lee¹, John E Dominy², Yoon Jong Choi³

¹1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

|May 30, 2014

Resumen

La insulina utiliza proteínas del ciclo celular como la ciclina D1-Cdk4 para controlar los niveles de glucosa mediante la regulación de la acetilación de PGC-1α y la producción de glucosa hepática, ofreciendo nuevas vías de tratamiento de la diabetes.

Área de la Ciencia:

Regulación del metabolismo.
El control del ciclo celular de control del ciclo celular.
Investigación de la diabetes en la investigación de la diabetes.

Sus antecedentes:

La insulina es clave para la homeostasis de la glucosa; su desregulación causa diabetes.
PGC-1α vincula la señalización de la insulina con la expresión génica metabólica.
GCN5 y sirtuina 1 regulan la actividad de PGC-1α a través de la acetilación.

Objetivo del estudio:

Investigar el papel de la maquinaria del ciclo celular en las acciones metabólicas de la insulina.
Identificar los mecanismos moleculares que vinculan la señalización de la insulina al metabolismo de la glucosa.
Explorar objetivos terapéuticos para la diabetes.

Principales métodos:

Los modelos de ratón son modelos de ratón.
Sección química de alto rendimiento basada en células para el cribado químico.
Análisis bioquímicos para medir la acetilación y la actividad de la quinasa.

Principales resultados:

La insulina activa la ciclina D1-Cdk4, aumentando la actividad de GCN5 y suprimiendo la producción de glucosa.
Un inhibidor de Cdk4 reduce la acetilación de PGC-1α.
La pérdida de ciclina D1 causa hiperglucemia; su activación normaliza la glucosa en sangre en modelos diabéticos.

Conclusiones:

La insulina utiliza los componentes del ciclo celular (ciclina D1-Cdk4) para regular la homeostasis de la glucosa en las células post-mitóticas.
Esta vía controla la acetilación de PGC-1α y la producción hepática de glucosa.
Dirigirse a la ciclina D1-Cdk4 ofrece una nueva estrategia para el manejo de la diabetes.

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