Publication in detail

J Biol Chem 2010 Nov 26;285(48):37198-209. Epub 2010 Sep

Whole Body Deletion of AMP-activated Protein Kinase β2 Reduces Muscle AMPK Activity and Exercise Capacity

Campbell, DJ; Chen, ZP; Dzamko, NL; Galic, S; Hewitt, K; Honeyman, J; Jorgensen, SB; Kemp, BE.; Koentgen, F; Koopman, R; Lynch, GS; Naim, T; O', ; Neill, HM; Schertzer, JD; Scott, J; Steinberg, GR; Vandenderen, BJ; Watt, MJ

Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.

AMP-activated protein kinase (AMPK) subunits ( 1 and 2) provide scaffolds for binding and subunits and contain a carbohydrate-binding module important for regulating enzyme activity. We generated C57Bl/6 mice with germline deletion of AMPK 2 ( 2 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 2 KO mice are viable and breed normally. 2 KO mice had a reduction in skeletal muscle AMPK 1 and 2 expression despite up-regulation of the 1 isoform. Heart AMPK 2 expression was also reduced but this did not affect resting AMPK 1 or 2 activities. AMPK 1 and 2 activities were not changed in liver, fat, or hypothalamus. AICAR-stimulated glucose uptake but not fatty acid oxidation was impaired in 2 KO mice. During treadmill running 2 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 2 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 2 KO mice gained more weight and were more susceptible to the development of hyperinsulinemia and glucose intolerance. In summary these data show that deletion of AMPK 2 reduces AMPK activity in skeletal muscle resulting in impaired exercise capacity and the worsening of diet-induced obesity and glucose intolerance.

» Online Version

Proven Track Record

The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 400 scientific publications are based on research using Ozgene mice.

Go to Publications

Global Client Base

Ozgene generates genetically customised mice for researchers around the world. Ozgene mice can be found in 31 different countries on 5 continents from small academic institutions to multinational pharmaceutical companies.

See Client Papers

Lean Management

Ozgene is applying Lean Management principles to deliver the highest quality services and shortest lead times to our customers. The implementation of Lean Culture has already seen an improvement in our processes and timelines.

Read More