Endurance training-induced changes in insulin sensitivity and gene expression

The beneficial effects of regular physical activity on insulin sensitivity (SO 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 [S.sub.I] 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. [S.sub.I] index was derived from a frequently sampled intravenous glucose tolerance test using MINMOD Millennium software. Sixteen subjects were selected: eight showing no changes in [S.sub.I] (low responders, L[S.sub.1]R) and eight displaying marked improvement in [S.sub.I] (high responders, H[S.sub.I]R) with ET. The [S.sub.I] increase was about four times greater in H[S.sub.I]R compared with L[S.sub.I]R (+3.6 [+ or -] 0.5 vs. -1.2 [+ or -] 0.5 [micro]U*[ml.sup.-1] * [min.sup.-1], mean [+ or -] SE), whereas age, body mass index, percent body fat, and baseline [S.sub.I] were similar between the groups. Triplicate microarrays were performed, comparing pooled RNA with H[S.sub.I]R and L[S.sub.I]R 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 H[S.sub.I]R and L[S.sub.I]R 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 H[S.sub.I]R 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. microarray; MINMOD Millennium; exercise training