Metabolic signatures suggest o-phosphocholine to UDP-N-acetylglucosamine ratio as a potential biomarker for high-glucose and/or palmitate exposure in pancreatic β-cells

Metabolic signatures suggest o-phosphocholine to UDP-N-acetylglucosamine ratio as a potential... Introduction Chronic exposure to high-glucose and free fatty acids (FFA) alone/or in combination; and the resulting gluco-, lipo- and glucolipo-toxic conditions, respectively, have been known to induce dysfunction and apoptosis of β-cells in Diabe- tes. The molecular mechanisms and the development of biomarkers that can be used to predict similarities and differences behind these conditions would help in easier and earlier diagnosis of Diabetes. Objectives This study aims to use metabolomics to gain insight into the mechanisms by which β-cells respond to excess- nutrient stress and identify associated biomarkers. Methods INS-1E cells were cultured in high-glucose, palmitate alone/or in combination for 24 h to mimic gluco-, lipo- and glucolipo-toxic conditions, respectively. Biochemical and cellular experiments were performed to confirm the establish- ment of these conditions. To gain molecular insights, abundant metabolites were identified and quantified using H-NMR. Results No loss of cellular viability was observed in high-glucose while exposure to FFA alone/in combination with high- glucose was associated with increased ROS levels, membrane damage, lipid accumulation, and DNA double-strand breaks. Forty-nine abundant metabolites were identified and quantified using H-NMR. Chemometric pair-wise analysis in gluco- toxic and lipotoxic conditions, when compared with glucolipotoxic conditions, revealed partial overlap in the dysregulated metabolites; however, the http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Metabolomics Springer Journals

Metabolic signatures suggest o-phosphocholine to UDP-N-acetylglucosamine ratio as a potential biomarker for high-glucose and/or palmitate exposure in pancreatic β-cells

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Publisher
Springer Journals
Copyright
Copyright © 2019 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Life Sciences; Biochemistry, general; Molecular Medicine; Cell Biology; Developmental Biology; Biomedicine, general
ISSN
1573-3882
eISSN
1573-3890
D.O.I.
10.1007/s11306-019-1516-3
Publisher site
See Article on Publisher Site

Abstract

Introduction Chronic exposure to high-glucose and free fatty acids (FFA) alone/or in combination; and the resulting gluco-, lipo- and glucolipo-toxic conditions, respectively, have been known to induce dysfunction and apoptosis of β-cells in Diabe- tes. The molecular mechanisms and the development of biomarkers that can be used to predict similarities and differences behind these conditions would help in easier and earlier diagnosis of Diabetes. Objectives This study aims to use metabolomics to gain insight into the mechanisms by which β-cells respond to excess- nutrient stress and identify associated biomarkers. Methods INS-1E cells were cultured in high-glucose, palmitate alone/or in combination for 24 h to mimic gluco-, lipo- and glucolipo-toxic conditions, respectively. Biochemical and cellular experiments were performed to confirm the establish- ment of these conditions. To gain molecular insights, abundant metabolites were identified and quantified using H-NMR. Results No loss of cellular viability was observed in high-glucose while exposure to FFA alone/in combination with high- glucose was associated with increased ROS levels, membrane damage, lipid accumulation, and DNA double-strand breaks. Forty-nine abundant metabolites were identified and quantified using H-NMR. Chemometric pair-wise analysis in gluco- toxic and lipotoxic conditions, when compared with glucolipotoxic conditions, revealed partial overlap in the dysregulated metabolites; however, the

Journal

MetabolomicsSpringer Journals

Published: Mar 29, 2019

References

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