Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals

Abstract Measurement of glycated hemoglobin (HbA1c) in human red blood cells plays a critical role in the diagnosis and treatment of diabetes mellitus. However, recent studies have suggested large variation in the relationship between average glucose levels and HbA1c, creating the need to understand...

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Main Authors: Joel D. Paprocki, Patrick J. Macdonald, Yongjin Xu, Alan Cheng, Timothy C. Dunn, Sergey Y. Tetin
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-74574-3
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author Joel D. Paprocki
Patrick J. Macdonald
Yongjin Xu
Alan Cheng
Timothy C. Dunn
Sergey Y. Tetin
author_facet Joel D. Paprocki
Patrick J. Macdonald
Yongjin Xu
Alan Cheng
Timothy C. Dunn
Sergey Y. Tetin
author_sort Joel D. Paprocki
collection DOAJ
description Abstract Measurement of glycated hemoglobin (HbA1c) in human red blood cells plays a critical role in the diagnosis and treatment of diabetes mellitus. However, recent studies have suggested large variation in the relationship between average glucose levels and HbA1c, creating the need to understand glucose variability at the cellular level. Here, we devised a fluorescence-based method to quantitatively observe GLUT1-mediated intracellular glucose analog tracer uptake in individual RBCs utilizing microfluidics and confocal microscopy. For the first time, we demonstrate that intracellular/extracellular tracer percentages can be measured at the single cell level using the fluorescently labeled glucose analog, 2-NBDG. A small donor panel study indicates that the characteristic intracellular 2-NBDG percentages can statistically differ based on race (i.e., Caucasian/Hispanic vs Black). RBC intracellular glucose analog tracer 2-NBDG levels show significant variability both from cell-to-cell and from donor-to-donor. This specific transport mechanism will affect HbA1c formation in erythrocytes. This finding further supports a more personalized, and perhaps improved, diagnostic strategy for diabetes.
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institution Kabale University
issn 2045-2322
language English
publishDate 2025-01-01
publisher Nature Portfolio
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series Scientific Reports
spelling doaj-art-2621aab1b0fd45f48897e181748e603e2025-01-26T12:30:42ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-024-74574-3Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individualsJoel D. Paprocki0Patrick J. Macdonald1Yongjin Xu2Alan Cheng3Timothy C. Dunn4Sergey Y. Tetin5Applied Research and Technology, Abbott Diagnostics Division, Abbott LaboratoriesApplied Research and Technology, Abbott Diagnostics Division, Abbott LaboratoriesClinical Affairs, Abbott Diabetes Care IncClinical Affairs, Abbott Diabetes Care IncClinical Affairs, Abbott Diabetes Care IncApplied Research and Technology, Abbott Diagnostics Division, Abbott LaboratoriesAbstract Measurement of glycated hemoglobin (HbA1c) in human red blood cells plays a critical role in the diagnosis and treatment of diabetes mellitus. However, recent studies have suggested large variation in the relationship between average glucose levels and HbA1c, creating the need to understand glucose variability at the cellular level. Here, we devised a fluorescence-based method to quantitatively observe GLUT1-mediated intracellular glucose analog tracer uptake in individual RBCs utilizing microfluidics and confocal microscopy. For the first time, we demonstrate that intracellular/extracellular tracer percentages can be measured at the single cell level using the fluorescently labeled glucose analog, 2-NBDG. A small donor panel study indicates that the characteristic intracellular 2-NBDG percentages can statistically differ based on race (i.e., Caucasian/Hispanic vs Black). RBC intracellular glucose analog tracer 2-NBDG levels show significant variability both from cell-to-cell and from donor-to-donor. This specific transport mechanism will affect HbA1c formation in erythrocytes. This finding further supports a more personalized, and perhaps improved, diagnostic strategy for diabetes.https://doi.org/10.1038/s41598-024-74574-3ErythrocytesDemographicHbA1cDiabetesContinuous glucose monitoringIntracellular
spellingShingle Joel D. Paprocki
Patrick J. Macdonald
Yongjin Xu
Alan Cheng
Timothy C. Dunn
Sergey Y. Tetin
Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals
Scientific Reports
Erythrocytes
Demographic
HbA1c
Diabetes
Continuous glucose monitoring
Intracellular
title Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals
title_full Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals
title_fullStr Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals
title_full_unstemmed Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals
title_short Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals
title_sort quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals
topic Erythrocytes
Demographic
HbA1c
Diabetes
Continuous glucose monitoring
Intracellular
url https://doi.org/10.1038/s41598-024-74574-3
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