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
Metabolomics – Springer Journals
Published: Mar 29, 2019
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