Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha
Experimental & Molecular Medicine
;
: 535-543, 2007.
Artículo
en Inglés
| WPRIM
| ID: wpr-174049
ABSTRACT
Insufficient intracellular fat oxidation is an important contributor to aging-related insulin resistance, while the precise mechanism underlying is unclear. AMP-activated protein kinase (AMPK) is an important regulator of intracellular fat oxidation and was evidenced to play a key role in high-glucose and high-fat induced glucose intolerance. In the present study, we investigated whether altered AMPK expression or activity was also involved in aging-related insulin resistance. Insulin sensitivity of rats' skeletal muscles was evaluated using in-vitro glucose uptake assay. Activity of alpha subunit of AMPK (AMPKalpha) was evaluated by measuring the phosphorylation of both AMPKalpha (P-AMPKalpha) and acetyl-CoA carboxylase (P-ACC), while expression of AMPKalpha was assessed by determining the mRNA levels of AMPKalpha1 and AMPKalpha2, and protein contents of AMPKalpha. Compared with 4-month old rats, 24-month old rats exhibited obviously impaired insulin sensitivity. At the same time, AMPKalpha activity significantly decreased, while AMPKalpha expression did not alter during aging. Glucose transporter 4 expression also decreased in old rats. Compared with 24-month old rats, administration of the specific activator of AMPK, 5-aminoimidazole-4-carboxamide riboside (AICAR), significantly elevated AMPKalpha activity and GluT4 expression. Also, aging-related insulin resistance was significantly ameliorated by AICAR treatment. In conclusion, aging-related insulin resistance is associated with impaired AMPKalpha activity and could be ameliorated by AICAR, thus indicating a possible role of AMPK in aging-induced insulin resistance.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fosforilación
/
Acetil-CoA Carboxilasa
/
Ribonucleótidos
/
Envejecimiento
/
Resistencia a la Insulina
/
Ratas Wistar
/
Proteínas Serina-Treonina Quinasas
/
Músculo Esquelético
/
Transportador de Glucosa de Tipo 4
/
Proteínas Quinasas Activadas por AMP
Límite:
Animales
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2007
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS