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

Exp Mol Med. 2007 Aug 31;39(4):535-43. doi: 10.1038/emm.2007.59.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase / metabolism
  • Aging / physiology*
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Glucose / metabolism*
  • Glucose Transporter Type 4 / metabolism
  • Insulin / blood*
  • Insulin Resistance*
  • Male
  • Multienzyme Complexes / antagonists & inhibitors*
  • Multienzyme Complexes / metabolism
  • Muscle, Skeletal / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Ribonucleotides / pharmacology

Substances

  • Glucose Transporter Type 4
  • Insulin
  • Multienzyme Complexes
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase
  • AICA ribonucleotide
  • Glucose