TY - JOUR
T1 - Endurance training-induced changes in insulin sensitivity and gene expression
AU - Teran-Garcia, Margarita
AU - Rankinen, Tuomo
AU - Koza, Robert A.
AU - Rao, D. C.
AU - Bouchard, Claude
PY - 2005/6
Y1 - 2005/6
N2 - The beneficial effects of regular physical activity on insulin sensitivity (SI) and glucose tolerance are well documented, with considerable heterogeneity in responsiveness to exercise training (ET). To find novel candidate genes for ET-induced improvement in SI, we used microarray technology. Total RNA was isolated from vastus lateralis muscle before and after 20 wk of exercise from individuals participating in the HERITAGE Family Study. SI index was derived from a frequently sampled intravenous glucose tolerance test using MINMOD Millennium software. Sixteen subjects were selected: eight showing no changes in SI (low responders, LSIR) and eight displaying marked improvement in SI (high responders, HS IR) with ET. The ST increase was about four times greater in HSIR compared with LSIR (+3.6 ± 0.5 vs. - 1.2 ± 0.5 μU·ml-1, mean ± SE), whereas age, body mass index, percent body fat, and baseline SI were similar between the groups. Triplicate microarrays were performed, comparing pooled RNA with HSIR and LSIR individuals for differences in gene expression before and after ET using in situ-generated microarrays (18, 861 genes). Array data were validated by quantitative RT-PCR. Almost twice as many genes showed at least twofold differences between HSIR and LS IR after training compared with pretraining. We identified differentially expressed genes involved in energy metabolism and signaling, novel structural genes, and transcripts of unknown function. Genes of interest upregulated in HSIR include V-Ski oncogene, four-and-a-half LIM domain 1, and titin. Further study of these novel candidate genes should provide a better understanding of molecular mechanisms involved in the improvement in insulin sensitivity in response to regular exercise.
AB - The beneficial effects of regular physical activity on insulin sensitivity (SI) and glucose tolerance are well documented, with considerable heterogeneity in responsiveness to exercise training (ET). To find novel candidate genes for ET-induced improvement in SI, we used microarray technology. Total RNA was isolated from vastus lateralis muscle before and after 20 wk of exercise from individuals participating in the HERITAGE Family Study. SI index was derived from a frequently sampled intravenous glucose tolerance test using MINMOD Millennium software. Sixteen subjects were selected: eight showing no changes in SI (low responders, LSIR) and eight displaying marked improvement in SI (high responders, HS IR) with ET. The ST increase was about four times greater in HSIR compared with LSIR (+3.6 ± 0.5 vs. - 1.2 ± 0.5 μU·ml-1, mean ± SE), whereas age, body mass index, percent body fat, and baseline SI were similar between the groups. Triplicate microarrays were performed, comparing pooled RNA with HSIR and LSIR individuals for differences in gene expression before and after ET using in situ-generated microarrays (18, 861 genes). Array data were validated by quantitative RT-PCR. Almost twice as many genes showed at least twofold differences between HSIR and LS IR after training compared with pretraining. We identified differentially expressed genes involved in energy metabolism and signaling, novel structural genes, and transcripts of unknown function. Genes of interest upregulated in HSIR include V-Ski oncogene, four-and-a-half LIM domain 1, and titin. Further study of these novel candidate genes should provide a better understanding of molecular mechanisms involved in the improvement in insulin sensitivity in response to regular exercise.
KW - Exercise training
KW - MINMOD Millennium
KW - Microarray
UR - http://www.scopus.com/inward/record.url?scp=19444365803&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00467.2004
DO - 10.1152/ajpendo.00467.2004
M3 - Article
C2 - 15687108
AN - SCOPUS:19444365803
SN - 0193-1849
VL - 288
SP - E1168-E1178
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 6 51-6
ER -