title: Effect of acute activation of 5'-AMP-activated protein kinase on glycogen regulation in isolated rat skeletal muscle.
abstract: 5'-AMP-activated protein kinase (AMPK) has been implicated in glycogen metabolism in skeletal muscle. However, the physiological relevance of increased AMPK activity during exercise has not been fully clarified. This study was performed to determine the direct effects of acute AMPK activation on muscle glycogen regulation. For this purpose, we used an isolated rat muscle preparation and pharmacologically activated AMPK with 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR). Tetanic contraction in vitro markedly activated the alpha(1)- and alpha(2)-isoforms of AMPK, with a corresponding increase in the rate of 3-O-methylglucose uptake. Incubation with AICAR elicited similar enhancement of AMPK activity and 3-O-methylglucose uptake in rat epitrochlearis muscle. In contrast, whereas contraction stimulated glycogen synthase (GS), AICAR treatment decreased GS activity. Insulin-stimulated GS activity also decreased after AICAR treatment. Whereas contraction activated glycogen phosphorylase (GP), AICAR did not alter GP activity. The muscle glycogen content decreased in response to contraction but was unchanged by AICAR. Lactate release was markedly increased when muscles were stimulated with AICAR in buffer containing glucose, indicating that the glucose taken up into the muscle was catabolized via glycolysis. Our results suggest that AMPK does not mediate contraction-stimulated glycogen synthesis or glycogenolysis in skeletal muscle and also that acute AMPK activation leads to an increased glycolytic flux by antagonizing contraction-stimulated glycogen synthesis.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Licht
authors.initials: L
authors.lastname: Miyamoto
authors.forename: Taro
authors.initials: T
authors.lastname: Toyoda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shin
authors.initials: S
authors.lastname: Yonemitsu
authors.forename: Masako
authors.initials: M
authors.lastname: Nakano
authors.forename: Satsuki
authors.initials: S
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D055372:AMP-Activated Protein Kinases; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012263:Ribonucleosides; D012265:Ribonucleotides; D013997:Time Factors
chemical_list: D007328:Insulin; D009097:Multienzyme Complexes; D012263:Ribonucleosides; D012265:Ribonucleotides; D019344:Lactic Acid; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D000255:Adenosine Triphosphate; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose