%0 Journal Article
%T Gain of function AMP坼activated protein kinase 污3 mutation (AMPK
污3R200Q) in pig muscle increases glycogen storage regardless of AMPK activation
%A David E. Gerrard
%A Peter J. Roach
%A Sungkwon Park
%A Tracy L. Scheffler
%J Archive of "Physiological Reports".
%D 2016
%R 10.14814/phy2.12802
%X Chronic activation of AMP坼activated protein kinase (AMPK) increases glycogen content in skeletal muscle. Previously, we demonstrated that a mutation in the ryanodine receptor (RyR1R615C) blunts AMPK phosphorylation in longissimus muscle of pigs with a gain of function mutation in the AMPK 污3 subunit (AMPK 污3R200Q); this may decrease the glycogen storage capacity of AMPK 污3R200Q + RyR1R615C muscle. Therefore, our aim in this study was to utilize our pig model to understand how AMPK 污3R200Q and AMPK activation contribute to glycogen storage and metabolism in muscle. We selected and bred pigs in order to generate offspring with naturally occurring AMPK 污3R200Q, RyR1R615C, and AMPK 污3R200Q + RyR1R615C mutations, and also retained wild坼type littermates (control). We assessed glycogen content and parameters of glycogen metabolism in longissimus muscle. Regardless of RyR1R615C, AMPK 污3R200Q increased the glycogen content by approximately 70%. Activity of glycogen synthase (GS) without the allosteric activator glucose 6坼phosphate (G6P) was decreased in AMPK 污3R200Q relative to all other genotypes, whereas both AMPK 污3R200Q and AMPK 污3R200Q + RyR1R615C muscle exhibited increased GS activity with G6P. Increased activity of GS with G6P was not associated with increased abundance of GS or hexokinase 2. However, AMPK 污3R200Q enhanced UDP坼glucose pyrophosphorylase 2 (UGP2) expression approximately threefold. Although UGP2 is not generally considered a rate坼limiting enzyme for glycogen synthesis, our model suggests that UGP2 plays an important role in increasing flux to glycogen synthase. Moreover, we have shown that the capacity for glycogen storage is more closely related to the AMPK 污3R200Q mutation than activity
%K Calcium
%K glucose 6 phosphate
%K glycogen synthase
%K skeletal muscle
%K UDP坼glucose pyrophosphorylase
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908487/