title: A transcriptional signature of "exercise resistance" in skeletal muscle of individuals with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Exercise benefits most, but not all, individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to determine whether a proportion of individuals with T2DM would fail to demonstrate exercise-induced metabolic improvements. We hypothesized that this lack of response would be related to their skeletal muscle transcriptional profile.
  
  
  METHODS
  42 participants with T2DM from the previously reported HART-D study underwent a 9-month supervised exercise intervention. We performed a principal components analysis to distinguish Responders from Non-Responders (n=9 each) based on: decreases in (1) HbA1c, (2) %fat (3) BMI and (4) increase in skeletal muscle mtDNA. mRNA expression patterns in muscle tissue at baseline were assessed by microarray and qRT-PCR analysis in both groups.
  
  
  RESULTS
  Of 186 genes identified by microarray analysis, 70% were up-regulated in Responders and down-regulated in Non-Responders. Several genes involved in substrate metabolism and mitochondrial biogenesis were significantly different (fold-change>1.5, p<0.05) between the groups at baseline, indicating a blunted oxidative capacity at baseline in Non-Responders.
  
  
  CONCLUSIONS
  These data suggest that a unique baseline expression pattern of genes involved in muscle fuel metabolism may predict an individual's lack of exercise response in metabolic outcomes, thus allowing exercise interventions to be targeted to these individuals and aid in the identification of novel approaches to treat Non-Responders in the future.
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA; Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL, USA.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Stephens
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA; Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Pennington Biomedical Research Center, Department of Preventive Medicine, Baton Rouge, LA, USA; Louisiana State University, Department of Kinesiology, Baton Rouge, LA, USA.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Johannsen
authors.affiliation: Pennington Biomedical Research Center, Department of Preventive Medicine, Baton Rouge, LA, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Church
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA; Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA; Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL, USA. Electronic address: Lauren.Sparks@flhosp.org.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Sparks
mesh_terms: D000328:Adult; D015992:Body Mass Index; D004272:DNA, Mitochondrial / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology*; D015444:Exercise; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D006442:Glycated Hemoglobin
keywords: Exercise resistance; Gene expression; Human skeletal muscle; Type 2 diabetes mellitus