Role of Pyruvate Dehydrogenase Kinase 4 in Regulation of Blood Glucose Levels / 당뇨병
Korean Diabetes Journal
;
: 274-283, 2010.
Artículo
en Inglés
| WPRIM
| ID: wpr-176330
ABSTRACT
In the well-fed state a relatively high activity of the pyruvate dehydrogenase complex (PDC) reduces blood glucose levels by directing the carbon of pyruvate into the citric acid cycle. In the fasted state a relatively low activity of the PDC helps maintain blood glucose levels by conserving pyruvate and other three carbon compounds for gluconeogenesis. The relative activities of the pyruvate dehydrogenase kinases (PDKs) and the opposing pyruvate dehydrogenase phosphatases determine the activity of PDC in the fed and fasted states. Up regulation of PDK4 is largely responsible for inactivation of PDC in the fasted state. PDK4 knockout mice have lower fasting blood glucose levels than wild type mice, proving that up regulation of PDK4 is important for normal glucose homeostasis. In type 2 diabetes, up regulation of PDK4 also inactivates PDC, which promotes gluconeogenesis and thereby contributes to the hyperglycemia characteristic of this disease. When fed a high fat diet, wild type mice develop fasting hyperglycemia but PDK4 knockout mice remain euglycemic, proving that up regulation of PDK4 contributes to hyperglycemia in diabetes. These finding suggest PDK4 inhibitors might prove useful in the treatment of type 2 diabetes.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Oxidorreductasas
/
Fosfotransferasas
/
Proteínas Quinasas
/
Complejo Piruvato Deshidrogenasa
/
Glucemia
/
Carbono
/
Regulación hacia Arriba
/
Ayuno
/
Ciclo del Ácido Cítrico
/
Proteínas Serina-Treonina Quinasas
Límite:
Animales
Idioma:
Inglés
Revista:
Korean Diabetes Journal
Año:
2010
Tipo del documento:
Artículo
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