title: Genetic model for the chronic activation of skeletal muscle AMP-activated protein kinase leads to glycogen accumulation.
abstract: The AMP-activated protein kinase (AMPK) is an important metabolic sensor/effector that coordinates many of the changes in mammalian tissues during variations in energy availability. We have sought to create an in vivo genetic model of chronic AMPK activation, selecting murine skeletal muscle as a representative tissue where AMPK plays important roles. Muscle-selective expression of a mutant noncatalytic gamma1 subunit (R70Qgamma) of AMPK activates AMPK and increases muscle glycogen content. The increase in glycogen content requires the presence of the endogenous AMPK catalytic alpha-subunit, since the offspring of cross-breeding of these mice with mice expressing a dominant negative AMPKalpha subunit have normal glycogen content. In R70Qgamma1-expressing mice, there is a small, but significant, increase in muscle glycogen synthase (GSY) activity associated with an increase in the muscle expression of the liver isoform GSY2. The increase in glycogen content is accompanied, as might be expected, by an increase in exercise capacity. Transgene expression of this mutant AMPKgamma1 subunit may provide a useful model for the chronic activation of AMPK in other tissues to clarify its multiple roles in the regulation of metabolism and other physiological processes.
authors.affiliation: Department of Medicine, Dartmouth Medical School, Dartmouth College, Hanover, NH 03755-3833, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Barré
authors.forename: Christine
authors.initials: C
authors.lastname: Richardson
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: Joseph
authors.initials: J
authors.lastname: Brozinick
authors.forename: Steven
authors.initials: S
authors.lastname: Fiering
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
authors.forename: Lee A
authors.initials: LA
authors.lastname: Witters
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008957:Models, Genetic; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes
chemical_list: D009097:Multienzyme Complexes; C526224:Prkag1 protein, mouse; D006003:Glycogen; D006006:Glycogen Synthase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases