PDPR Gene Expression Correlates with Exercise-Training Insulin Sensitivity Changes.
PURPOSE: Whole body insulin sensitivity (Si) typically improves following aerobic exercise training; however, individual responses can be highly variable. The purpose of this study was to use global gene expression to identify skeletal muscle genes that correlate with exercise-induced Si changes. METHODS: Longitudinal cohorts from the Studies of Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) were utilized as Discovery (Affymetrix) and Confirmation (Illumina) of vastus lateralis gene expression profiles. Discovery (n=39; 21 men) and Confirmation (n=42; 19 men) cohorts were matched for age (52 ± 8 vs. 51 ± 10 yr), BMI (30.4 ± 2.8 vs. 29.7 ± 2.8 kg*m), and VO2max (30.4 ± 2.8 vs. 29.7 ± 2.8 mL/kg/min). Si was determined via intravenous glucose tolerance test pre- and post-training. Pearson product-moment correlation coefficients determined relationships between a) baseline and b) training-induced changes in gene expression and %ΔSi after training. RESULTS: Expression of 2454 (Discovery) and 1778 genes (Confirmation) at baseline were significantly (P<0.05) correlated to %ΔSi; 112 genes overlapped. Pathway analyses identified Ca-signaling-related transcripts in this 112-gene list. Expression changes of 1384 (Discovery) and 1288 genes (Confirmation) following training were significantly (P<0.05) correlated to %ΔSi; 33 genes overlapped, representing contractile apparatus of skeletal and smooth muscle genes. Pyruvate dehydrogenase phosphatase regulatory subunit (PDPR) expression at baseline (p=0.01, r=0.41) and post-training (p=0.01, r=0.43) were both correlated with %ΔSi. CONCLUSION: Exercise-induced adaptations in skeletal muscle Si are related to baseline levels of Ca-regulating transcripts, which may prime the muscle for adaptation. Relationships between %ΔSi and PDPR, a regulatory subunit of the pyruvate dehydrogenase complex, indicate that the Si response is strongly related to key steps in metabolic regulation.
Barberio, MD; Huffman, KM; Giri, M; Hoffman, EP; Kraus, WE; Hubal, MJ
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