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Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKα

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 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 AMPKα1 and AMPKα2, 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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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Qiang, W., Weiqiang, K., Qing, Z. et al. Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKα. Exp Mol Med 39, 535–543 (2007). https://doi.org/10.1038/emm.2007.59

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Keywords

  • 5'-AMP-activated protein kinase
  • aging
  • glucose transporter type 4
  • insulin resistance
  • muscle, skeletal
  • rat

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