Exp Mol Med.  2007 Aug;39(4):535-543.

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

• Qiang W
• Weiqiang K
• Qing Z
• Pengju Z
• Yi L

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.

Keyword

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

MeSH Terms

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