title: Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles.
abstract: Epinephrine increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown, and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated in condition with decreased GS activation. Saline or epinephrine (0.02 mg/100 g rat) was injected subcutaneously in Wistar rats (∼130 g) with low (24-h-fasted), normal (normal diet), and high glycogen content (fasted-refed), and epitrochlearis muscles were removed after 3 h and incubated ex vivo, eliminating epinephrine action. Epinephrine injection reduced glycogen content in epitrochlearis muscles with high (120.7 ± 17.8 vs. 204.6 ± 14.5 mmol/kg, P < 0.01) and normal glycogen (89.5 ± 7.6 vs. 152 ± 8.1 mmol/kg, P < 0.01), but not significantly in muscles with low glycogen (90.0 ± 5.0 vs. 102.8 ± 7.8 mmol/kg, P = 0.17). In saline-injected rats, GS phosphorylation at sites 2+2a, 3a+3b, and 1b was higher and GS activity lower in muscles with high compared with low glycogen. GS sites 2+2a and 3a+3b phosphorylation decreased and GS activity increased in muscles where epinephrine decreased glycogen content; these parameters were unchanged in epitrochlearis from fasted rats where epinephrine injection did not decrease glycogen content. Incubation with insulin decreased GS site 3a+3b phosphorylation independently of glycogen content. Insulin-stimulated glucose uptake was increased in muscles where epinephrine injection decreased glycogen content. In conclusion, epinephrine stimulates glycogenolysis in epitrochlearis muscles with normal and high, but not low, glycogen content. Epinephrine-stimulated glycogenolysis decreased GS phosphorylation and increased GS activity. These data for the first time document direct regulation of GS phosphorylation by glycogen content.
authors.affiliation: Charles University Third Faculty of Medicine, Prague, Czech Republic;
authors.forename: Anders J
authors.initials: AJ
authors.lastname: Kolnes
authors.affiliation: Molecular Physiology Group, The August Krogh Centre, Department of Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark;
authors.forename: Jesper B
authors.initials: JB
authors.lastname: Birk
authors.affiliation: National Institute of Occupational Health, Oslo, Norway; and.
authors.forename: Einar
authors.initials: E
authors.lastname: Eilertsen
authors.affiliation: National Institute of Occupational Health, Oslo, Norway; and.
authors.forename: Jorid T
authors.initials: JT
authors.lastname: Stuenæs
authors.affiliation: Molecular Physiology Group, The August Krogh Centre, Department of Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark;
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
authors.affiliation: Molecular Physiology Group, The August Krogh Centre, Department of Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark; Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway jorgen.jensen@nih.no.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jensen
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004032:Diet; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007328:Insulin; D006003:Glycogen; D006006:Glycogen Synthase; D005947:Glucose; D004837:Epinephrine
keywords: AMPK; Cori cycle; GSK3; TBC1D4; diabetes; insulin sensitivity; liver; phosphorylation