Exercise Increases Glucose Transporter-4 Levels on Peripheral Blood Mononuclear Cells

AbstractPURPOSEGlucose transporter 4 (GLUT4) plays a key role in the pathophysiology of type 2 diabetes. GLUT4 is upregulated in response to exercise, enhancing cellular glucose transport in skeletal muscle tissue. This mechanism appears to remain intact in individuals with insulin resistance. Details of the mechanism are poorly understood and are challenging to study due to the invasive nature of muscle biopsy. Peripheral blood mononuclear cells (PBMC) have documented insulin-sensitive GLUT4 activity and may serve as a proxy tissue for studying skeletal muscle GLUT4. The purpose of this study was to investigate whether GLUT4 in PBMC is affected by conditioning.METHODWe recruited sixteen student athletes from the cross-country running and skiing teams and fifteen sedentary students matched for age and sex from the University of Alaska Fairbanks. PMBC were collected with mononuclear cell separation tubes. GLUT4 concentrations were measured using a commercially available enzyme linked immunosorbant assay. Additionally, correlations between PBMC GLUT4 and common indicators of insulin resistance were examined.RESULTSResults indicate significantly higher PBMC GLUT4 levels in conditioned athletes than in their sedentary counterparts, similar to what has been documented in myocytes. Females were observed to have higher PBMC GLUT4 levels than males. Correlations were not detected between PBMC GLUT4 and hemoglobin A1c (HbA1c), glucose, insulin, HOMA-IR, BMI, or body fat.CONCLUSIONThis study provides evidence to support exploration of PBMC as a proxy tissue for studying GLUT4 response to exercise or other non-insulin factors. PURPOSE Glucose transporter 4 (GLUT4) plays a key role in the pathophysiology of type 2 diabetes. GLUT4 is upregulated in response to exercise, enhancing cellular glucose transport in skeletal muscle tissue. This mechanism appears to remain intact in individuals with insulin resistance. Details of the mechanism are poorly understood and are challenging to study due to the invasive nature of muscle biopsy. Peripheral blood mononuclear cells (PBMC) have documented insulin-sensitive GLUT4 activity and may serve as a proxy tissue for studying skeletal muscle GLUT4. The purpose of this study was to investigate whether GLUT4 in PBMC is affected by conditioning. METHOD We recruited sixteen student athletes from the cross-country running and skiing teams and fifteen sedentary students matched for age and sex from the University of Alaska Fairbanks. PMBC were collected with mononuclear cell separation tubes. GLUT4 concentrations were measured using a commercially available enzyme linked immunosorbant assay. Additionally, correlations between PBMC GLUT4 and common indicators of insulin resistance were examined. RESULTS Results indicate significantly higher PBMC GLUT4 levels in conditioned athletes than in their sedentary counterparts, similar to what has been documented in myocytes. Females were observed to have higher PBMC GLUT4 levels than males. Correlations were not detected between PBMC GLUT4 and hemoglobin A1c (HbA1c), glucose, insulin, HOMA-IR, BMI, or body fat. CONCLUSION This study provides evidence to support exploration of PBMC as a proxy tissue for studying GLUT4 response to exercise or other non-insulin factors. Corresponding author: Kriya L Dunlap, University of Alaska Fairbanks, Department of Chemistry and Biochemistry, 900 Yukon Drive, Fairbanks, AK 99775, kldunlap@alaska.edu Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM103395. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank Scarlett Hopkins of the University of Alaska Fairbanks for conducting blood draws, and the Center for Alaska Native Health Research for the use of clinic space (NIH/NGMS COBRE Grant P30GM103325). There are no conflicts of interest to declare. The results of this study are presented clearly, honestly and without fabrication, falsification or inappropriate data manipulation. The results of this study do not constitute endorsement by ACSM. Accepted for Publication: 15 December 2017 © 2017 American College of Sports Medicine

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