Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha - PubMed (original) (raw)

. 2007 Aug 31;39(4):535-43.

doi: 10.1038/emm.2007.59.

Affiliations

• PMID: 17934342
• DOI: 10.1038/emm.2007.59

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

Wan Qiang et al. Exp Mol Med. 2007.

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.

PubMed Disclaimer

Similar articles

• High-fat diet feeding impairs both the expression and activity of AMPKa in rats' skeletal muscle.
  Liu Y, Wan Q, Guan Q, Gao L, Zhao J. Liu Y, et al. Biochem Biophys Res Commun. 2006 Jan 13;339(2):701-7. doi: 10.1016/j.bbrc.2005.11.068. Epub 2005 Nov 21. Biochem Biophys Res Commun. 2006. PMID: 16316631
• Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles.
  Jessen N, Pold R, Buhl ES, Jensen LS, Schmitz O, Lund S. Jessen N, et al. J Appl Physiol (1985). 2003 Apr;94(4):1373-9. doi: 10.1152/japplphysiol.00250.2002. Epub 2002 Dec 20. J Appl Physiol (1985). 2003. PMID: 12496137
• Rosiglitazone treatment enhances acute AMP-activated protein kinase-mediated muscle and adipose tissue glucose uptake in high-fat-fed rats.
  Ye JM, Dzamko N, Hoy AJ, Iglesias MA, Kemp B, Kraegen E. Ye JM, et al. Diabetes. 2006 Oct;55(10):2797-804. doi: 10.2337/db05-1315. Diabetes. 2006. PMID: 17003345
• AMP-activated protein kinase and muscle glucose uptake.
  Musi N, Goodyear LJ. Musi N, et al. Acta Physiol Scand. 2003 Aug;178(4):337-45. doi: 10.1046/j.1365-201X.2003.01168.x. Acta Physiol Scand. 2003. PMID: 12864738 Review.
• AMP-activated protein kinase: possible target for treatment of type 2 diabetes.
  Winder WW. Winder WW. Diabetes Technol Ther. 2000 Autumn;2(3):441-8. doi: 10.1089/15209150050194305. Diabetes Technol Ther. 2000. PMID: 11467346 Review.

Cited by

• 8-Prenylgenistein Isoflavone in Cheonggukjang Acts as a Novel AMPK Activator Attenuating Hepatic Steatosis by Enhancing the SIRT1-Mediated Pathway.
  Arulkumar R, Jung HJ, Noh SG, Kim HW, Chung HY. Arulkumar R, et al. Int J Mol Sci. 2024 Sep 8;25(17):9730. doi: 10.3390/ijms25179730. Int J Mol Sci. 2024. PMID: 39273677 Free PMC article.
• Obesity in the elderly: is faulty metabolism to blame?
  Johannsen DL, Ravussin E. Johannsen DL, et al. Aging health. 2010 Apr 1;6(2):159-167. doi: 10.2217/ahe.10.12. Aging health. 2010. PMID: 20563222 Free PMC article.
• The coordination of nuclear and mitochondrial communication during aging and calorie restriction.
  Finley LW, Haigis MC. Finley LW, et al. Ageing Res Rev. 2009 Jul;8(3):173-88. doi: 10.1016/j.arr.2009.03.003. Epub 2009 Mar 27. Ageing Res Rev. 2009. PMID: 19491041 Free PMC article. Review.
• Relationships Between Ion Channels, Mitochondrial Functions and Inflammation in Human Aging.
  Strickland M, Yacoubi-Loueslati B, Bouhaouala-Zahar B, Pender SLF, Larbi A. Strickland M, et al. Front Physiol. 2019 Mar 1;10:158. doi: 10.3389/fphys.2019.00158. eCollection 2019. Front Physiol. 2019. PMID: 30881309 Free PMC article. Review.
• Dysregulated Autophagy Mediates Sarcopenic Obesity and Its Complications via AMPK and PGC1α Signaling Pathways: Potential Involvement of Gut Dysbiosis as a Pathological Link.
  Ryu JY, Choi HM, Yang HI, Kim KS. Ryu JY, et al. Int J Mol Sci. 2020 Sep 19;21(18):6887. doi: 10.3390/ijms21186887. Int J Mol Sci. 2020. PMID: 32961822 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Medical

  • MedlinePlus Health Information