葡萄糖和谷氨酰胺的非同步代谢在胰岛素分泌中的作用:模型方法

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biophysical chemistry Pub Date : 2024-05-23 DOI:10.1016/j.bpc.2024.107270
Vladimir Grubelnik , Jan Zmazek , Marko Gosak , Marko Marhl
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引用次数: 0

摘要

我们提出了一个详细的β细胞计算模型,强调在葡萄糖和葡萄糖-谷氨酰胺刺激下无机代谢的作用。该模型超越了传统的线粒体氧化磷酸化和 ATP 敏感的 K+ 通道,强调在 KATP 通道附近主要由磷酸烯醇丙酮酸生成 ATP。该模型还强调了 H2O2 作为信号分子在葡萄糖刺激胰岛素分泌第一阶段的调节作用。在第二阶段,该模型强调了葡萄糖刺激通过丙酮酸羧化酶和谷氨酰胺通过谷氨酸脱氢酶激活的无动力通路的关键作用。它特别强调了 NADPH 和谷氨酸的产生是胰岛素分泌的关键促进因素。该模型的预测与经验数据一致,突出了代谢途径之间复杂的相互作用,强调了葡萄糖在胰岛素分泌中的主要作用和谷氨酰胺的促进作用。通过描述这些关键的代谢途径,该模型为糖尿病的潜在治疗目标提供了宝贵的见解。
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The role of anaplerotic metabolism of glucose and glutamine in insulin secretion: A model approach

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.

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来源期刊
Biophysical chemistry
Biophysical chemistry 生物-生化与分子生物学
CiteScore
6.10
自引率
10.50%
发文量
121
审稿时长
20 days
期刊介绍: Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.
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