title: Reduced skeletal muscle AMPK and mitochondrial markers do not promote age-induced insulin resistance.
abstract: In both rodents and humans, aging-associated reductions in skeletal muscle AMP-activated protein kinase (AMPK) activity and mitochondrial function have been linked to the development of skeletal muscle insulin resistance. However, whether reductions in skeletal muscle AMPK and mitochondrial capacity actually precipitate the development of aging-induced insulin resistance is not known. Mice lacking both isoforms of the AMPK β-subunit in skeletal muscle (AMPK-MKO) have no detectable AMPK activity and are characterized by large reductions in exercise capacity, mitochondrial content, and contraction-stimulated glucose uptake making them an ideal model to determine whether reductions in AMPK and mitochondrial content promote the development of aging-induced insulin resistance. In the current study we find that a lack of skeletal muscle AMPK results in a life-long reduction in mitochondrial activity but does not affect body mass, body composition, glucose tolerance, or insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp in mice of old age (18 mo). These data demonstrate that reductions in skeletal muscle AMPK and mitochondrial activity do not cause the development of age-induced insulin resistance.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Ontario, Canada;
authors.forename: Adam L
authors.initials: AL
authors.lastname: Bujak
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Ontario, Canada;
authors.forename: Regje M E
authors.initials: RM
authors.lastname: Blümer
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Ontario, Canada;
authors.forename: Katarina
authors.initials: K
authors.lastname: Marcinko
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Ontario, Canada;
authors.forename: Morgan D
authors.initials: MD
authors.lastname: Fullerton
authors.affiliation: St. Vincent's Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Ontario, Canada; Faculty of Health Sciences, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada; and gsteinberg@mcmaster.ca.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Steinberg
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D005951:Glucose Tolerance Test / Q000379:methods; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007328:Insulin; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK-β1β2 muscle KO mice; mitochondria; obesity