title: Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes.
abstract: 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.
authors.affiliation: 1Research Center for Genetic Medicine, Children's National Medical Center, Durham, NC; 2Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC; 3Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC; 4Department of Exercise and Nutrition Sciences, George Washington University, WASHINGTON, DC; 5Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC; and 6Department of Integrative Systems Biology, George Washington University, Washington, DC.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Barberio
authors.forename: Kim M
authors.initials: KM
authors.lastname: Huffman
authors.forename: Mamta
authors.initials: M
authors.lastname: Giri
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Hubal
mesh_terms: D020013:Calcium Signaling; D002318:Cardiovascular Diseases / Q000517:prevention & control; D015444:Exercise / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000235:genetics*; D012307:Risk Factors; D057185:Sedentary Behavior
chemical_list: D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase