The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective.
Changes in eating habits and sedentary lifestyle are main contributors to type 2 diabetes (T2D) development, and studies suggest that epigenetic modifications are involved with the growing incidence of this disease. Regular exercise modulates many intracellular pathways improving insulin resistance and glucose uptake in skeletal muscle, both early abnormalities of T2D. Mitochondria dysfunction and decreased expression of glucose transporter (GLUT4) were identified as main factors of insulin resistance. Moreover, it has been suggested that skeletal muscle of T2D subjects have a different pattern of epigenetic marks on the promoter of GLUT4 and PGC1, main regulator of mitochondrial function, compared with nondiabetic individuals. Recent studies have proposed that regular exercise could improve glucose uptake by the attenuation of such epigenetic modification induced at GLUT4, PGC1 and its downstream regulators; however, the exact mechanism is still to be understood. Herein we review the known epigenetic modifications on GLUT4 and mitochondrial proteins that lead to impairment of skeletal muscle glucose uptake and T2D development, and the effect of physical exercise at these modifications.
Federal University of Goiás, Regional Jataí, Jataí, GO, Brazil; Detroit R&D, Research Department, Detroit, MI, USA. Electronic address: jmsantos@detroitrandd.com.
Júlia Matzenbacher
JM
Dos Santos
Federal University of Goiás, Regional Jataí, Jataí, GO, Brazil.
Marcos Lazaro
ML
Moreli
Dr. Ram Manohar Lohia, Institute of Medical Science, Lucknow, India.
Shikha
S
Tewari
Federal University of Goiás, Regional Jataí, Jataí, GO, Brazil; Detroit R&D, Research Department, Detroit, MI, USA. Electronic address: sandrabenite@ufg.br.
Sandra Aparecida
SA
Benite-Ribeiro
D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015444:Exercise; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000502:physiology
D051275:Glucose Transporter Type 4; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D005947:Glucose
Epigenetic modification; GLUT4; Mitochondria; Physical exercise; Type 2 diabetes