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• W1985156983 startingPage "2583" @default.
• W1985156983 abstract "Chronic exposure to hyperglycaemic conditions has been shown to have detrimental effects on beta cell function. The resulting glucotoxicity is a contributing factor to the development of type 2 diabetes. The objective of this study was to combine a metabolomics approach with functional assays to gain insight into the mechanism by which glucotoxicity exerts its effects. The BRIN-BD11 and INS-1E beta cell lines were cultured in 25 mM glucose for 20 h to mimic glucotoxic effects. PDK-2 protein expression, intracellular glutathione levels and the change in mitochondrial membrane potential and intracellular calcium following glucose stimulation were determined. Metabolomic analysis of beta cell metabolite extracts was performed using GC–MS, 1H NMR and 13C NMR. Conditions to mimic glucotoxicity were established and resulted in no loss of cellular viability in either cell line while causing a decrease in insulin secretion. Metabolomic analysis of beta cells following exposure to high glucose revealed a change in amino acids, an increase in glucose and a decrease in phospho-choline, n−3 and n−6 PUFAs during glucose stimulated insulin secretion relative to cells cultured under control conditions. However, no changes in calcium handling or mitochondrial membrane potential were evident. Results indicate that a decrease in TCA cycle metabolism in combination with an alteration in fatty acid composition and phosphocholine levels may play a role in glucotoxicity induced impairment of glucose stimulated insulin secretion. Alterations in certain metabolic pathways play a role in glucotoxicity in the pancreatic beta cell." @default.
• W1985156983 created "2016-06-24" @default.
• W1985156983 creator A5003874766 @default.
• W1985156983 creator A5015075333 @default.
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• W1985156983 date "2013-03-01" @default.
• W1985156983 modified "2023-10-07" @default.
• W1985156983 title "Metabolomic analysis of pancreatic beta cells following exposure to high glucose" @default.
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• W1985156983 doi "https://doi.org/10.1016/j.bbagen.2012.10.025" @default.
• W1985156983 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23153904" @default.
• W1985156983 hasPublicationYear "2013" @default.
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