Gain of function AMP-activated protein kinase gamma 3 mutation (AMPK gamma 3(R200Q)) in pig muscle increases glycogen storage regardless of AMPK activation

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dc.contributor.authorScheffler, Tracy L.en
dc.contributor.authorPark, Sungkwonen
dc.contributor.authorRoach, Peter J.en
dc.contributor.authorGerrard, David E.en
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2019-08-28T16:26:07Zen
dc.date.available2019-08-28T16:26:07Zen
dc.date.issued2016-06en
dc.description.abstractChronic activation of AMP-activated protein kinase (AMPK) increases glycogen content in skeletal muscle. Previously, we demonstrated that a mutation in the ryanodine receptor (RyR1(R615C)) blunts AMPK phosphorylation in longissimus muscle of pigs with a gain of function mutation in the AMPK gamma 3 subunit (AMPK gamma 3(R200Q)); this may decrease the glycogen storage capacity of AMPK gamma 3(R200Q) + RyR1(R615C) muscle. Therefore, our aim in this study was to utilize our pig model to understand how AMPK gamma 3(R200Q) 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 gamma 3(R200Q), RyR1(R615C), and AMPK gamma 3(R200Q) + RyR1(R615C) mutations, and also retained wild-type littermates (control). We assessed glycogen content and parameters of glycogen metabolism in longissimus muscle. Regardless of RyR1(R615C), AMPK gamma 3(R200Q) increased the glycogen content by approximately 70%. Activity of glycogen synthase (GS) without the allosteric activator glucose 6-phosphate (G6P) was decreased in AMPK gamma 3(R200Q) relative to all other genotypes, whereas both AMPK gamma 3(R200Q) and AMPK gamma 3(R200Q) + RyR1(R615C) 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 gamma 3(R200Q) enhanced UDP-glucose pyrophosphorylase 2 (UGP2) expression approximately threefold. Although UGP2 is not generally considered a rate-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 gamma 3(R200Q) mutation than activity.en
dc.description.sponsorshipNINDS NIH HHS [R01 NS056454]; NIDDK NIH HHS [R01 DK027221]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.14814/phy2.12802en
dc.identifier.issn2051-817Xen
dc.identifier.issue11en
dc.identifier.otherUNSP e12802en
dc.identifier.pmid27302990en
dc.identifier.urihttp://hdl.handle.net/10919/93283en
dc.identifier.volume4en
dc.language.isoenen
dc.publisherThe Physiological Societyen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCalciumen
dc.subjectglucose 6 phosphateen
dc.subjectglycogen synthaseen
dc.subjectskeletal muscleen
dc.subjectUDP-glucose pyrophosphorylaseen
dc.titleGain of function AMP-activated protein kinase gamma 3 mutation (AMPK gamma 3(R200Q)) in pig muscle increases glycogen storage regardless of AMPK activationen
dc.title.serialPhysiological Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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