Impairments in Site-Specific AS160 Phosphorylation and Effects of Exercise Training

  1. Joseph A. Houmard2,8
  1. 1Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute, Diabetes Institute, Ohio University, Athens, Ohio
  2. 2Department of Kinesiology, Human Performance Laboratory, East Carolina University, Greenville, North Carolina
  3. 3Division of Endocrinology, Metabolism and Lipids, Department of Internal Medicine, Emory University, Atlanta, Georgia
  4. 4Department of Pediatrics, Brody School of Medicine at East Carolina University, Greenville, North Carolina
  5. 5Section of Endocrinology & Metabolism, Department of Internal Medicine, Brody School of Medicine at East Carolina University, Greenville, North Carolina
  6. 6Molecular Physiology Group, The August Krogh Centre, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
  7. 7Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  8. 8East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina.
  1. Corresponding author: Leslie A. Consitt, consitt{at}ohio.edu.

Abstract

The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18–84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation. A euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed in 73 individuals encompassing a wide age range (18–84 years of age), and insulin-stimulated AS160 phosphorylation was determined. Decrements in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666, and phospho-Akt substrate, but not Ser-318 or Ser-751. Twelve weeks of endurance- or strength-oriented exercise training increased whole-body insulin action and reversed impairments in AS160 phosphorylation evident in insulin-resistant aged individuals. These findings suggest that a dampening of insulin-induced phosphorylation of AS160 on specific sites in skeletal muscle contributes to the insulin resistance evident in a sedentary aging population and that exercise training is an effective intervention for treating these impairments.

Footnotes

  • Received February 8, 2013.
  • Accepted June 17, 2013.

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  1. Diabetes vol. 62 no. 10 3437-3447
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