RT Journal Article
SR Electronic
T1 Impairments in Site-Specific AS160 Phosphorylation and Effects of Exercise Training
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 3437
OP 3447
DO 10.2337/db13-0229
VO 62
IS 10
A1 Consitt, Leslie A.
A1 Van Meter, Jessica
A1 Newton, Christopher A.
A1 Collier, David N.
A1 Dar, Moahad S.
A1 Wojtaszewski, Jørgen F.P.
A1 Treebak, Jonas T.
A1 Tanner, Charles J.
A1 Houmard, Joseph A.
YR 2013
UL http://diabetes.diabetesjournals.org/content/62/10/3437.abstract
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 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.