The role of anaplerotic metabolism of glucose and glutamine in insulin secretion: A model approach

• DOI: 10.1016/j.bpc.2024.107270
• Publication Date: 2024-05-23T18:39:16Z
• Authors: Vladimir Grubelnik; Jan Zmazek; Marko Gosak; Marko Marhl
• Keywords: Carbohydrate Metabolism

We propose a detailed computational beta cell model that emphasizes the role of anaplerotic metabolism under glucose and glucose-glutamine stimulation. This goes beyond traditional focus on mitochondrial oxidative phosphorylation ATP-sensitive K+ channels, highlighting predominant generation ATP from phosphoenolpyruvate in vicinity KATP channels. It also underlines modulatory H2O2 as signaling molecule first phase glucose-stimulated insulin secretion. In second phase, critical pathways, activated by stimulation via pyruvate carboxylase glutamine glutamate dehydrogenase. particularly focuses production NADPH key enhancers The predictions are consistent with empirical data, complex interplay metabolic pathways emphasizing primary facilitating By delineating these crucial provides valuable insights into potential therapeutic targets for diabetes.