Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes.


Journal Article

Whole body insulin sensitivity (Si) typically improves after aerobic exercise training; however, individual responses can be highly variable. The purpose of this study was to use global gene expression to identify skeletal muscle genes that correlate with exercise-induced Si changes.Longitudinal cohorts from the Studies of Targeted Risk Reduction Intervention through Defined Exercise were used as Discovery (Affymetrix) and Confirmation (Illumina) of vastus lateralis gene expression profiles. Discovery (n = 39; 21 men) and Confirmation (n = 42; 19 men) cohorts were matched for age (52 ± 8 vs 51 ± 10 yr), body mass index (30.4 ± 2.8 vs 29.7 ± 2.8 kg·m), and V˙O2max (30.4 ± 2.8 vs 29.7 ± 2.8 mL·kg·min). Si was determined via intravenous glucose tolerance test pretraining and posttraining. Pearson product-moment correlation coefficients determined relationships between a) baseline and b) training-induced changes in gene expression and %ΔSi after training.Expression of 2454 (Discovery) and 1778 genes (Confirmation) at baseline were significantly (P < 0.05) correlated to %ΔSi; 112 genes overlapped. Pathway analyses identified Ca signaling-related transcripts in this 112-gene list. Expression changes of 1384 (Discovery) and 1288 genes (Confirmation) after training were significantly (P < 0.05) correlated to %ΔSi; 33 genes overlapped, representing contractile apparatus of skeletal and smooth muscle genes. Pyruvate dehydrogenase phosphatase regulatory subunit expression at baseline (P = 0.01, r = 0.41) and posttraining (P = 0.01, r = 0.43) were both correlated with %ΔSi.Exercise-induced adaptations in skeletal muscle Si are related to baseline levels of Ca-regulating transcripts, which may prime the muscle for adaptation. Relationships between %ΔSi and pyruvate dehydrogenase phosphatase regulatory, a regulatory subunit of the pyruvate dehydrogenase complex, indicate that the Si response is strongly related to key steps in metabolic regulation.

Full Text

Duke Authors

Cited Authors

  • Barberio, MD; Huffman, KM; Giri, M; Hoffman, EP; Kraus, WE; Hubal, MJ

Published Date

  • December 2016

Published In

Volume / Issue

  • 48 / 12

Start / End Page

  • 2387 - 2397

PubMed ID

  • 27846149

Pubmed Central ID

  • 27846149

Electronic International Standard Serial Number (EISSN)

  • 1530-0315

International Standard Serial Number (ISSN)

  • 0195-9131

Digital Object Identifier (DOI)

  • 10.1249/MSS.0000000000001041


  • eng