Gene Mutation Thought To Control Energy Levels Discovered

Including patients at The Ottawa Hospital, this study focused on the gene for AMPK (adenosine monophosphate-activated protein kinase), which controls the amount of energy in our cells by becoming active when fuel stores start to deplete, such as during exercise. The mutation discovered in individuals from two unrelated families caused a doubling of AMPK activity in muscle during rest, mimicking a state of exercise.

The uOttawa-Ottawa Hospital research team led by Drs.  Mary-Ellen Harper, Robert Dent and Ruth McPherson, in collaboration with researchers in Berkeley California, also found that the mutation produces a decrease in the storage in muscle of fat and an increase in muscle glycogen. The discovery has implications for the treatment of type 2 diabetes, as high levels of fat stored in the muscle have been linked to insulin resistance.

In addition, as metformin, a drug commonly used to both prevent and treat diabetes, acts by increasing AMPK activity, this discovery provides valuable information for pharmaceutical research.  The findings will also be of great interest to exercise physiologists, as increased muscle glycogen enhances a person’s capacity for endurance exercise (e.g., marathon running).

This significant discovery, made possible by grants from the Heart & Stroke Foundation of Ontario is reported in the journal, PLoS One.

Citation: Costford SR, Kavaslar N, Ahituv N, Chaudhry SN, Schackwitz WS, et al (2007) Gain-of-Function R225W Mutation in Human AMPKc3 Causing Increased Glycogen and Decreased Triglyceride in Skeletal Muscle. PLoS One 2(9): e903. doi:10.1371/journal.pone.0000903