Low‐intensity exercise increases skeletal muscle protein expression of PPARδ and UCP3 in type 2 diabetic patients

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Abstract
Background Physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. We tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients. Methods We determined mRNA expression of 20 selected genes following a self-supervised program of walking (> 150 min per week) over a 4-month period. Results This level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (HOMA)). Skeletal muscle mRNA expression of Cbl-associated protein (CAP), diacylglycerol kinase (DGK)δ, CAP, uncoupling protein (UCP) 3, nuclear respiratory factor (NRF)-1, and peroxisome proliferator-activated receptor (PPAR)δ tended to increase in type 2 diabetic patients with an improved clinical profile. Skeletal muscle protein expression of PPARδ and UCP3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters. Conclusions This study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. Moreover, the positive clinical response to exercise is correlated with changes in skeletalmuscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes. Copyright © 2006 John Wiley & Sons, Ltd.