Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation.

The effects of Task-Oriented Motor Training on gait characteristics of patients with type 2 diabetes neuropathy.

BACKGROUND: It is known that general gait training improves lower extremity muscle strength and endurance in Diabetes Neuropathy (DN). But, it is still unknown whether Task-Oriented (TO) gait training would change gait biomechanics and the risk of falling in DN. TO gait training focuses on promoting timing and coordination of lower extremity movements through goal-directed practices with sufficient repetition. METHODS: A group of 14 patients with DN participated in a time-series study. All subjects participated in four sessions of assessments (Initial, Pre, Post and Follow-Up). Training was twice a week for 12 weeks. Vertical and horizontal Ground Reaction Forces (GRF), Time Get up and Go (TGUG) and Fall Efficacy Scale-International (FES-I) were evaluated. Gait training started with stepping patterns that progressively changed to complicated patterns of walking. Then, training continued combining walking patterns with upper extremity activities and then ended with treadmill-paced practice. RESULTS: DN patients significantly increased Second Vertical Peak Force and Horizontal Propulsive Force in addition decrease in Minimum Vertical Force. TGUG significantly decreased while FES-I reflected significant increase after gait training. DISCUSSION: Conclusively, training not only improved gait performance, confidence in daily activities and attenuated risk of falling, but also helped DN patients to improve feet biomechanics, muscles timing and coordination. CONCLUSIONS: Gait training with respect to principles of motor learning allowed patients to effectively improve through sessions.