Impairments in site-specific AS160 phosphorylation and effects of exercise training

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.
OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind62
Udgave nummer10
Sider (fra-til)3437-3447
Antal sider11
ISSN0012-1797
DOI
StatusUdgivet - 2013

Bibliografisk note

CURIS 2013 NEXS 174

ID: 49037081