Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha.
- Author:
Wan QIANG
1
;
Kang WEIQIANG
;
Zhu QING
;
Zhang PENGJU
;
Liu YI
Author Information
1. Department of Internal Medicine, Shandong Provincial Hospital Shandong University, Jinan 250021, China. liuyishanyi@yahoo.com.cn
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
5'-AMP-activated protein kinase;
aging;
glucose transporter type 4;
insulin resistance;
muscle, skeletal;
rat
- MeSH:
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
- From:Experimental & Molecular Medicine
2007;39(4):535-543
- CountryRepublic of Korea
- Language:English
-
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.
