Whole body deletion of AMP-activated protein kinase beta2 reduces muscle AMPK activity and exercise capacity

Gregory R Steinberg, Hayley M O'Neill, Nicolas L Dzamko, Sandra Galic, Tim Naim, Rene Koopman, Sebastian B Jorgensen, Jane E Honeyman, Kimberly Hewitt, Zhi -Ping Chen, Jonathan D Schertzer, John Scott, Frank Koentgen, Gordon S Lynch, Matthew J Watt, Bryce J W van Denderen, Duncan J Campbell, Bruce E Kemp

Research output: Contribution to journalArticleResearchpeer-review

109 Citations (Scopus)


AMPK beta subunits (beta1 and beta2) provide scaffolds for binding alpha and gamma subunits and contain a carbohydrate-binding module important for regulating enzyme activity. We generated C57Bl/6 mice with germline deletion of AMPK beta2 (beta2 KO) and examined AMPK expression and activity, exercise capacity, metabolic control during muscle contractions, aminoimidazole carboxamide ribonucleotide (AICAR) sensitivity and susceptibility to obesity-induced insulin resistance. We find that beta2 KO mice are viable and breed normally. beta2 KO mice had a reduction in skeletal muscle AMPK alpha1 and alpha2 expression despite up regulation of the beta21 isoform. Heart AMPK alpha2 expression was also reduced but this did not affect resting AMPK alpha1 or alpha2 activities. AMPK alpha1 and alpha2 activities were not changed in liver, fat or hypothalamus. AICAR-stimulated glucose uptake but not fatty acid oxidation was impaired in beta2 KO mice. During treadmill running beta2 KO mice had reduced maximal and endurance exercise capacity which was associated with lower muscle and heart AMPK activity and reduced levels of muscle and liver glycogen. Reductions in exercise capacity of beta2 KO mice were not due to lower muscle mitochondrial content or defects in contraction-stimulated glucose uptake or fatty acid oxidation. When challenged with a high-fat diet beta2 KO mice gained more weight and were more susceptible to hyperinsulinemia and glucose intolerance. In summary these data show that deletion of AMPK beta2 reduces AMPK activity in skeletal muscle resulting in impaired exercise capacity and the worsening of diet-induced obesity and glucose intolerance.
Original languageEnglish
Pages (from-to)37198 - 37209
Number of pages11
JournalThe Journal of Biological Chemistry
Issue number48
Publication statusPublished - 2010

Cite this