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View full-text article in PMC

. 2022 Feb 15;298(4):101729. doi: 10.1016/j.jbc.2022.101729

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© 2022 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

Schematic illustrating the effect of G6pc2 KO on oxidative metabolism, energetics, and insulin secretion of βTC3 cells. Ablation of G6pc2 leads to increased glycolytic and citric acid cycle (CAC) flux. Cyclic flux through IDH and other putative NADPH-producing pathways is also upregulated along with an increase and a decrease in cytosolic(c) and mitochondrial(m) NADPH:NADP⁺ ratios, respectively. A combination of these metabolic perturbations, previously associated with increased GSIS (14), result in enhanced insulin production and release. Created with BioRender.com. GSIS, glucose-stimulated insulin secretion; IDH, isocitrate dehydrogenase.