Metabolomics data for: Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells

Walsby-Tickle, J; Haythorne, E; McCullagh, J; Ashcroft, F

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Metabolomics data for: Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells

Documentation:: These data support the paper "Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells". We have investigated the mechanism(s) by which chronic hyperglycaemia and diabetes lead to impaired β-cell metabolism and if this is linked to activation of mTORC1. We show that a glycolytic metabolite downstream of glucokinase and upstream of GAPDH mediates the effects of diabetes and chronic hyperglycemia on β-cell metabolism. This occurs, in part, through marked upregulation of mTORC1, which leads to changes in metabolic gene expression, oxidative phosphorylation and insulin secretion. AMPK is concomitantly downregulated. In addition, diabetes dramatically inhibits the activity of GAPDH and PDH, which impairs both glycolytic metabolism and entry into the TCA cycle. Our results support the idea that progressive impairment of β-cell metabolism, induced by increasing hyperglycaemia, speeds T2D development, and suggest that reducing glycolysis at the level of glucokinase may slow this progression. These data were produced from liquid chromatography-mass spectrometry analysis of: control and diabetic islets stimulated with 2 mM or 20 mM glucose (Fig. 3a,b & Suppl. Fig. 2), INS-1 (832/13) cells cultured for 48h with or without 5 μM koningic acid and subsequently stimulated with 2 mM or 20 mM glucose in the absence of koningic acid (Fig. 4a,b), and INS-1 cells cultured in 2 mM or 20 mM glucose (Suppl. Fig. 2). Anion-exchange chromatography-mass spectrometry (IC-MS) data were acquired on a Dionex IC-5000+ ion chromatography system hyphenated to a Thermo Fisher Scientific Q Exactive. Data are .zip compressed to reduce file size. Data files are in .raw format and require Thermo Fisher Scientific Xcalibur software to analyse.

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APA Style

Walsby-Tickle, J., Haythorne, E., McCullagh, J., & Ashcroft, F. (2022). Metabolomics data for: Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells. University of Oxford.

MLA Style

Walsby-Tickle, J., et al. Metabolomics Data for: Altered Glycolysis Triggers Impaired Mitochondrial Metabolism and mTORC1 Activation in Diabetic β-Cells. University of Oxford, 2022.

Chicago Style

Walsby-Tickle, J, E Haythorne, J McCullagh, and F Ashcroft. 2022. “Metabolomics Data for: Altered Glycolysis Triggers Impaired Mitochondrial Metabolism and mTORC1 Activation in Diabetic β-Cells.” University of Oxford.
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