Restoration of glucokinase expression in the liver normalizes postprandial glucose disposal in mice with hepatic deficiency of PDK1.
Diabetes
; 56(4): 1000-9, 2007 Apr.
Article
en En
| MEDLINE
| ID: mdl-17267763
Phosphoinositide-dependent kinase-1 (PDK1) is implicated in the metabolic effects of insulin as a key mediator of phosphoinositide 3-kinase-dependent signaling. Here we show that mice with liver-specific PDK1 deficiency manifest various defects in the metabolic actions of insulin in the liver as well as a type 2 diabetes-like phenotype characterized by marked hyperinsulinemia and postprandial hyperglycemia. The hepatic abundance of glucokinase, an important determinant of glucose flux and glucose-evoked signaling in hepatocytes, was substantially reduced in these mice. Restoration of hepatic glucokinase expression, with the use of an adenoviral vector, induced insulin-like effects in the liver and almost completely normalized the fasting hyperinsulinemia and postprandial hyperglycemia in these animals. These results indicate that, if the hepatic abundance of glucokinase is maintained, ingested glucose is normally disposed of even in the absence of acute activation of proximal insulin signaling, such as the activation of Akt, in the liver.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
/
Proteínas Serina-Treonina Quinasas
/
Glucoquinasa
/
Hígado
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
2007
Tipo del documento:
Article
Pais de publicación:
Estados Unidos