Abstract：
We propose a detailed computational beta cell model that emphasizes the role of anaplerotic metabolism under glucose and glucose-glutamine stimulation. This model goes beyond the traditional focus on mitochondrial oxidative phosphorylation and ATP-sensitive K+ channels, highlighting the predominant generation of ATP from phosphoenolpyruvate in the vicinity of KATP channels. It also underlines the modulatory role of H2O2 as a signaling molecule in the first phase of glucose-stimulated insulin secretion. In the second phase, the model emphasizes the critical role of anaplerotic pathways, activated by glucose stimulation via pyruvate carboxylase and by glutamine via glutamate dehydrogenase. It particularly focuses on the production of NADPH and glutamate as key enhancers of insulin secretion. The predictions of the model are consistent with empirical data, highlighting the complex interplay of metabolic pathways and emphasizing the primary role of glucose and the facilitating role of glutamine in insulin secretion. By delineating these crucial metabolic pathways, the model provides valuable insights into potential therapeutic targets for diabetes.
摘要：
我们提出了一个详细的计算β细胞模型，该模型强调了葡萄糖和葡萄糖-谷氨酰胺刺激下回补代谢的作用。该模型超越了传统的关注线粒体氧化磷酸化和ATP敏感的K+通道，突出了KATP通道附近磷酸烯醇丙酮酸主要产生ATP。它还强调了H2O2作为信号分子在葡萄糖刺激的胰岛素分泌的第一阶段的调节作用。在第二阶段,该模型强调了回补途径的关键作用，通过丙酮酸羧化酶的葡萄糖刺激和通过谷氨酸脱氢酶的谷氨酰胺激活。它特别关注NADPH和谷氨酸作为胰岛素分泌的关键增强剂的产生。模型的预测与经验数据一致，强调代谢途径的复杂相互作用，并强调葡萄糖的主要作用和谷氨酰胺在胰岛素分泌中的促进作用。通过描绘这些关键的代谢途径，该模型为糖尿病的潜在治疗靶点提供了有价值的见解.
