It's well and truly time to stop stating that AMPK regulates glucose uptake and fat oxidation <i>during</i> exercise
Glenn K. McConell
Abstract
In the late 1990s it was shown in vivo that skeletal muscle AMP-activated protein kinase (AMPK) activity is increased during exercise while pharmacological activation of AMPK could also increase skeletal muscle glucose uptake and free fatty acid (FFA) oxidation in vivo Taken together, these findings provided the impetus for the multitude of subsequent studies that have been undertaken to elucidate the role of AMPK in skeletal muscle metabolism. AMPK is a heterotrimer comprised of two -, two -, and three -subunits (8). The -subunits contain the catalytic domain responsible for activation, which, during contraction, occurs via an increase in cellular stress due to increases in AMP free and ADP free levels. The increase in AMP free allosterically activates AMPK and makes AMPK more susceptible to phosphorylation by upstream AMPK kinase(s), and the increase in AMP free and ADP free antagonizes the effect of protein phosphatases on AMPK, reducing the likelihood of dephosphorylation of AMPK (8, AMPK is activated during moderate or harder exercise in humans However, AMPK cannot simultaneously act as a primary regulator of both glucose uptake and FFA oxidation during exercise because there are situations (e.g., increases in exercise intensity, pre-versus posttraining exercise, high versus low carbohydrate diets) whereby increases in glucose uptake are accompanied by simultaneous decreases in fat oxidation and vice versa. Indeed, below I will discuss evidence that AMPK actually does not regulate either glucose uptake or fat oxidation during exercise.