Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha
Experimental & Molecular Medicine
;
: 535-543, 2007.
Article
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Acetyl-CoA Carboxylase
/
Ribonucleotides
/
Aging
/
Insulin Resistance
/
Rats, Wistar
/
Protein Serine-Threonine Kinases
/
Muscle, Skeletal
/
Glucose Transporter Type 4
/
AMP-Activated Protein Kinases
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2007
Type:
Article
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