title: Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects.
abstract: Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of Vo(2max)). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K(m) for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser(641), Ser(645), and Ser(645,649,653,657)), and phosphorylation of these sites remained decreased after 3.5 h; Ser⁷ phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K(m) for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.
authors.affiliation: Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jensen
authors.forename: Puntip
authors.initials: P
authors.lastname: Tantiwong
authors.forename: Jorid T
authors.initials: JT
authors.lastname: Stuenæs
authors.forename: Marjorie
authors.initials: M
authors.lastname: Molina-Carrion
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
mesh_terms: D000328:Adult; D001642:Bicycling; D001706:Biopsy; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D052097:Quadriceps Muscle / Q000201:enzymology* / Q000378:metabolism; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
chemical_list: D006003:Glycogen; D006006:Glycogen Synthase; D014532:Uridine Diphosphate Glucose