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Metabolomics

, 15:55 | Cite as

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

  • Saleem Yousf
  • Devika M. Sardesai
  • Abraham B. Mathew
  • Rashi Khandelwal
  • Jhankar D. Acharya
  • Shilpy SharmaEmail author
  • Jeetender ChughEmail author
Original Article
  • 200 Downloads

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 Diabetes. 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 establishment of these conditions. To gain molecular insights, abundant metabolites were identified and quantified using 1H-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 1H-NMR. Chemometric pair-wise analysis in glucotoxic and lipotoxic conditions, when compared with glucolipotoxic conditions, revealed partial overlap in the dysregulated metabolites; however, the dysregulation was more significant under glucolipotoxic conditions.

Conclusion

The current study compared gluco-, lipo- and glucolipotoxic conditions in parallel and elucidated differences in metabolic pathways that play major roles in Diabetes. o-phosphocholine and UDP-N-acetylglucosamine were identified as common dysregulated metabolites and their ratio was proposed as a potential biomarker for these conditions.

Keywords

Glucotoxicity Glucolipotoxicity Lipotoxicity Metabolic markers Pancreatic beta cell Type 2 diabetes mellitus 

Notes

Acknowledgements

The authors acknowledge HF-NMR facility at IISER-Pune (co-funded by DST-FIST and IISER Pune) and the flow cytometer facility at Institute for Applied Biological Research and Development, Pune. SY is thankful for the financial assistance from UGC-JRF, Government of India. JC acknowledges the funding from IISER Pune, Government of India. SS acknowledges the funding from Ramalingaswami fellowship (BT/RLF/Re-entry/11/2012; Department of Biotechnology — DBT, Government of India); University Grants Commission (UGC, Government of India F.4-5(18-FRP)(IV-Cycle)/2017(BSR)) and Board of College and University Development (BCUD) grant (SPPU). SS lab has been supported by Research and Development grant and DST-Purse grant to the Department of Biotechnology, SPPU; and UPE Phase II grant to SPPU. DMS is thankful for the financial assistance from DBT-JRF program and ABM acknowledges DBT, GOI for her Masters in Biotechnology fellowship. JDA acknowledges the funding from Start-up research grant by Science and Engineering Research board (SB/YS/LS-23/2014; SERB), Government of India. INS-1E cells were obtained as a kind gift from Prof. Claes Wollheim and Prof. Pierre Maechler, University Medical Centre, Geneva, Switzerland.

Author contributions

Conceived and designed the experiments: SS, JC. Performed the experiments: SY, DMS, ABM, RK, JDA, SS. Analysis and Interpretation of data: SY, JDA, SS, JC. Contributed reagents/materials/analysis tools: JDA, SS, JC. Compilation of data: SY, JDA, SS. Preparation of the manuscript: SS, JC. All authors have read and approved the final manuscript.

Funding

This study was funded by Ramalingaswami fellowship (BT/RLF/Re-entry/11/2012; Department of Biotechnology — DBT, Government of India) to SS; University Grants Commission (UGC, Government of India F.4-5(18-FRP)(IV-Cycle)/2017(BSR)) to SS; Board of College and University Development (BCUD) grant (SPPU) to SS; Start-up research grant by Science and Engineering Research board (SB/YS/LS-23/2014; SERB) to JDA; and funding from IISER Pune, Government of India to JC.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human and/or animal participants performed by any of the authors.

Supplementary material

11306_2019_1516_MOESM1_ESM.docx (2.7 mb)
Supplementary material 1 (DOCX 2776 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ChemistryIndian Institute of Science Education and Research (IISER) PunePuneIndia
  2. 2.Department of BiologyIndian Institute of Science Education and Research (IISER)PuneIndia
  3. 3.Department of BiotechnologySavitribai Phule Pune University (Formerly University of Pune)PuneIndia
  4. 4.Department of ZoologySavitribai Phule Pune University (Formerly University of Pune)PuneIndia

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