| Title: | The role of anaplerotic metabolism of glucose and glutamine in insulin secretion : a model approach |
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| Authors: | ID Grubelnik, Vladimir (Author)
ID Zmazek, Jan (Author)
ID Gosak, Marko (Author)
ID Marhl, Marko (Author) |
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| Files: |  RAZ_Grubelnik_Vladimir_2024.pdf (5,53 MB)
MD5: 9BE6724E24593D0E4240748D08D5F628
 https://www.sciencedirect.com/science/article/pii/S0301462224000991?via%3Dihub
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| Language: | English |
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| Work type: | Article |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | FERI - Faculty of Electrical Engineering and Computer Science
FNM - Faculty of Natural Sciences and Mathematics
MF - Faculty of Medicine
PEF - Faculty of Education
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| 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. |
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| Keywords: | mathematical models, pancreatic beta cell, pyruvate-malate cycle |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 31.01.2024 |
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| Article acceptance date: | 22.05.2024 |
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| Publication date: | 23.05.2024 |
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| Year of publishing: | 2024 |
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| Number of pages: | 16 str. |
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| Numbering: | Vol. 311, [article no.] 107270 |
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| PID: | 20.500.12556/DKUM-89024  |
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| UDC: | 612.015.3 |
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| ISSN on article: | 0301-4622 |
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| COBISS.SI-ID: | 197803779 |
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| DOI: | 10.1016/j.bpc.2024.107270 |
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| Publication date in DKUM: | 06.06.2024 |
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| Views: | 310 |
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| Downloads: | 52 |
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| Metadata: |    |
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| Categories: | Misc.
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