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 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.