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KMID : 0620920070390040535
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Experimental & Molecular Medicine
2007 Volume.39 No. 4 p.535 ~ p.543
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Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKα
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Qiang Wan
Weiqiang Kang
Pengju Zhang
Yi Liu
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Abstract
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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 α subunit of AMPK (AMPKα ) was evaluated by measuring the phosphorylation of both AMPKα (P- AMPKα ) and acetyl-CoA carboxylase (P-ACC), while expression of AMPKα was assessed by determining the mRNA levels of AMPKα 1 and AMPKα 2, and protein contents of AMPKα . Compared with 4-month old rats, 24-month old rats exhibited obviously impaired insulin sensitivity. At the same time, AMPKα activity significantly decreased, while AMPKα 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 AMPKα 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 AMPKα activity and could be ameliorated by AICAR, thus indicating a possible role of AMPK in aging-induced insulin resistance.
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KEYWORD
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5’-AMP-activated protein kinase, aging, glucose transporter type 4, insulin resistance, muscle, skeletal, rat
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