title: Gene and MicroRNA Expression Responses to Exercise; Relationship with Insulin Sensitivity.
abstract: BACKGROUND
  Healthy individuals on the lower end of the insulin sensitivity spectrum also have a reduced gene expression response to exercise for specific genes. The goal of this study was to determine the relationship between insulin sensitivity and exercise-induced gene expression in an unbiased, global manner.
  
  
  RESULTS
  Euglycemic clamps were used to measure insulin sensitivity and muscle biopsies were done at rest and 30 minutes after a single acute exercise bout in 14 healthy participants. Changes in mRNA expression were assessed using microarrays, and miRNA analysis was performed in a subset of 6 of the participants using sequencing techniques. Following exercise, 215 mRNAs were changed at the probe level (Bonferroni-corrected P<0.00000115). Pathway and Gene Ontology analysis showed enrichment in MAP kinase signaling, transcriptional regulation and DNA binding. Changes in several transcription factor mRNAs were correlated with insulin sensitivity, including MYC, r=0.71; SNF1LK, r=0.69; and ATF3, r= 0.61 (5 corrected for false discovery rate). Enrichment in the 5'-UTRs of exercise-responsive genes suggested regulation by common transcription factors, especially EGR1. miRNA species of interest that changed after exercise included miR-378, which is located in an intron of the PPARGC1B gene.
  
  
  CONCLUSIONS
  These results indicate that transcription factor gene expression responses to exercise depend highly on insulin sensitivity in healthy people. The overall pattern suggests a coordinated cycle by which exercise and insulin sensitivity regulate gene expression in muscle.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Carrie S
authors.initials: CS
authors.lastname: McLean
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Clinton
authors.initials: C
authors.lastname: Mielke
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: Cordova
authors.affiliation: Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Langlais
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bowen
authors.affiliation: Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors.forename: Danielle
authors.initials: D
authors.lastname: Miranda
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Dawn K
authors.initials: DK
authors.lastname: Coletta
authors.affiliation: School for the Science of Health Care Delivery, Arizona State University, Tempe, Arizona, United States of America; Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Mandarino
mesh_terms: D000328:Adult; D015444:Exercise / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D007328:Insulin; D035683:MicroRNAs