2267-PUB: Skeletal Muscle mRNA Transcriptional Signature of Response to Exercise of Patients in Different Stages of Glucose Tolerance

Abstract

Physical activity is an effective method to prevent and treat type 2 diabetes (T2D); however, the mechanisms of its beneficial effects have not been precisely elucidated. Skeletal muscle is a major contributor to overall glucose homeostasis in the body and is responsible for the efficacy of exercise intervention in the prevention and treatment of T2D. Currently, there is a lack of studies investigating the transcriptional signature of exercise training on skeletal muscles of patients with different stages of glucose tolerance. Thus, the aim of this study was to identify the mRNA signature of skeletal muscle adaptation to three-month exercise intervention in patients with different dysregulations of glucose metabolism. For this project we included 35 sedentary males, aged 24-65 years old, with BMI 26-33 kg/m2, divided into three groups: 15 normoglycemics, 12 prediabetics and 8 subjects with type 2 diabetes, treated with metformin only. RNA samples were obtained from biopsied Vastus lateralis muscles, before and after a 3-month supervised exercise intervention that occurred thrice weekly and consisted of mixed aerobic (60-70% of individual’s VO2max) and strength (60-70% of the repetition maximum for each exercise) activities. Selected groups of patients did not differ in age, BMI, number of performed trainings or diet during the intervention. mRNA sequencing was performed on an Illumina HiSeq 4000. We found highly significant differential mRNA expression in normoglycemics vs. T2D and prediabetic subjects, mostly related to mitochondrial processes, including the oxidative phosphorylation and thermogenesis pathways. Furthermore, we found that exercise intervention mostly affected these pathways, suggesting that a major defect of skeletal muscle in type 2 diabetes development is related to mitochondrial function and can be diminished by exercise. Disclosure L. Szczerbinski: None. M. Niemira: None. K. Szczerbinski: None. U. Puchta: None. A. Citko: None. E. Siewiec: None. J. Zapolska: None. M. Taylor: None. S. Larsen: None. M. Gorska: None. A. Kretowski: None. Funding Polish Diabetes Association; Polish Ministry of Science and Higher Education