Impairments in site-specific AS160 phosphorylation and effects of exercise training
Research output: Contribution to journal › Journal article › Research › peer-review
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 lifespan (18 to 84 years) 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 individuals encompassing a wide age range (n = 73, ages 18-84) and insulin-stimulated AS160 phosphorylation 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 (PAS), but not Ser-318 or Ser-751. Twelve weeks of either 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.
Original language | English |
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Journal | Diabetes |
Volume | 62 |
Issue number | 10 |
Pages (from-to) | 3437-3447 |
Number of pages | 11 |
ISSN | 0012-1797 |
DOIs | |
Publication status | Published - 2013 |
ID: 49037081