PMID- 26163877
OWN - NLM
STAT- MEDLINE
DCOM- 20151109
LR  - 20221207
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 64
IP  - 9
DP  - 2015 Sep
TI  - A transcriptional signature of "exercise resistance" in skeletal muscle of 
      individuals with type 2 diabetes mellitus.
PG  - 999-1004
LID - S0026-0495(15)00169-9 [pii]
LID - 10.1016/j.metabol.2015.06.008 [doi]
AB  - AIMS/HYPOTHESIS: 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/INTERPRETATIONS: 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Stephens, Natalie A
AU  - Stephens NA
AD  - 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.
FAU - Xie, Hui
AU  - Xie H
AD  - 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.
FAU - Johannsen, Neil M
AU  - Johannsen NM
AD  - Pennington Biomedical Research Center, Department of Preventive Medicine, Baton 
      Rouge, LA, USA; Louisiana State University, Department of Kinesiology, Baton 
      Rouge, LA, USA.
FAU - Church, Timothy S
AU  - Church TS
AD  - Pennington Biomedical Research Center, Department of Preventive Medicine, Baton 
      Rouge, LA, USA.
FAU - Smith, Steven R
AU  - Smith SR
AD  - 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.
FAU - Sparks, Lauren M
AU  - Sparks LM
AD  - 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.
LA  - eng
GR  - P30 DK072476/DK/NIDDK NIH HHS/United States
GR  - 2P30DK072476/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150616
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Glycated Hemoglobin A)
SB  - IM
MH  - Adult
MH  - Body Mass Index
MH  - DNA, Mitochondrial/metabolism
MH  - Diabetes Mellitus, Type 2/*genetics/*physiopathology
MH  - *Exercise
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Male
MH  - Muscle, Skeletal/*physiopathology
MH  - Regulatory Elements, Transcriptional/genetics
PMC - PMC5267524
MID - NIHMS841619
OTO - NOTNLM
OT  - Exercise resistance
OT  - Gene expression
OT  - Human skeletal muscle
OT  - Type 2 diabetes mellitus
COIS- There are no conflicts of interest.
EDAT- 2015/07/15 06:00
MHDA- 2015/11/10 06:00
PMCR- 2017/01/26
CRDT- 2015/07/13 06:00
PHST- 2015/04/22 00:00 [received]
PHST- 2015/06/05 00:00 [revised]
PHST- 2015/06/11 00:00 [accepted]
PHST- 2015/07/13 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/11/10 06:00 [medline]
PHST- 2017/01/26 00:00 [pmc-release]
AID - S0026-0495(15)00169-9 [pii]
AID - 10.1016/j.metabol.2015.06.008 [doi]
PST - ppublish
SO  - Metabolism. 2015 Sep;64(9):999-1004. doi: 10.1016/j.metabol.2015.06.008. Epub 
      2015 Jun 16.