Impairments in site-specific AS160 phosphorylation and effects of exercise training
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Impairments in site-specific AS160 phosphorylation and effects of exercise training. / Consitt, Leslie A; Van Meter, Jessica; Newton, Christopher A; Collier, David N; Dar, Moahad S; Wojtaszewski, Jørgen; Treebak, Jonas Thue; Tanner, Charles J; Houmard, Joseph A.
I: Diabetes, Bind 62, Nr. 10, 2013, s. 3437-3447.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Impairments in site-specific AS160 phosphorylation and effects of exercise training
AU - Consitt, Leslie A
AU - Van Meter, Jessica
AU - Newton, Christopher A
AU - Collier, David N
AU - Dar, Moahad S
AU - Wojtaszewski, Jørgen
AU - Treebak, Jonas Thue
AU - Tanner, Charles J
AU - Houmard, Joseph A
N1 - CURIS 2013 NEXS 174
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
U2 - 10.2337/db13-0229
DO - 10.2337/db13-0229
M3 - Journal article
C2 - 23801578
VL - 62
SP - 3437
EP - 3447
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 10
ER -
ID: 49037081