title: Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials.
abstract: Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases.
authors.affiliation: Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|Anschutz Health and Wellness Center, Division of Endocrinology, Metabolism and Diabetes, University of Colorado, Aurora, Colorado 80045, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bergouignan
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: Celine
authors.initials: C
authors.lastname: Latouche
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Heywood
authors.affiliation: Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Grace
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: Medini
authors.initials: M
authors.lastname: Reddy-Luthmoodoo
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: Alaina K
authors.initials: AK
authors.lastname: Natoli
authors.affiliation: Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|Department of Medicine, Monash University, Melbourne, Victoria 3800, Australia.|Behavioral Epidemiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|Melbourne School of Population Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.|School of Public Health, the University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Neville
authors.initials: N
authors.lastname: Owen
authors.affiliation: Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|Department of Medicine, Monash University, Melbourne, Victoria 3800, Australia.|School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125, Australia.|Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria 3800, Australia.|Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria 3000, Australia.|School of Sport Science, Exercise and Health, The University Of Western Australia, 35 Stirling Hwy, Crawley, Perth, Western Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Dunstan
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|Department of Medicine, Monash University, Melbourne, Victoria 3800, Australia.|Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia.|Department of Physiology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010766:Phosphorylation; D019518:Postprandial Period; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D057185:Sedentary Behavior
chemical_list: D001786:Blood Glucose; D020690:GTPase-Activating Proteins; D007328:Insulin; C518767:TBC1D4 protein, human; D051057:Proto-Oncogene Proteins c-akt; C000588423:ACACA protein, human; D000103:Acetyl-CoA Carboxylase; D005947:Glucose