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Diabetes. 2013 Oct;62(10):3437-47. doi: 10.2337/db13-0229. Epub 2013 Jun 25.

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

Author information

1
Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute, Diabetes Institute, Ohio University, Athens, Ohio.

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.

PMID:
23801578
PMCID:
PMC3781473
DOI:
10.2337/db13-0229
[Indexed for MEDLINE]
Free PMC Article

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