| Title: | Mitochondrial dysfunction in pancreatic alpha and beta cells associated with type 2 diabetes mellitus |
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| Authors: | ID Grubelnik, Vladimir (Author)
ID Zmazek, Jan (Author)
ID Markovič, Rene (Author)
ID Gosak, Marko (Author)
ID Marhl, Marko (Author) |
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| Files: |  RAZ_Grubelnik_Vladimir_2020.pdf (1,63 MB)
MD5: 715A06CE86DE8D71511B4477A6F3222E
 https://doi.org/10.3390/life10120348
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| Language: | English |
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| Work type: | Scientific work |
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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: | Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30-40% reduction in alpha cells' mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases. |
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| Keywords: | pancreatic endocrine cells, mathematical model, mitochondrial dysfunction, cellular bioenergetics, diabetes, glucagon, insulin |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 23.10.2020 |
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| Article acceptance date: | 10.12.2020 |
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| Publication date: | 14.12.2020 |
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| Publisher: | MDPI |
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| Year of publishing: | 2020 |
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| Number of pages: | Str. 1-16 |
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| Numbering: | Letn. 10, št. 12, št. članka 348 |
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| PID: | 20.500.12556/DKUM-90137  |
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| UDC: | 616.379 |
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| ISSN on article: | 2075-1729 |
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| COBISS.SI-ID: | 43234819 |
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| DOI: | 10.3390/life10120348 |
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| Publication date in DKUM: | 03.09.2024 |
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| Views: | 246 |
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| Downloads: | 21 |
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| Metadata: |    |
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| Categories: | Misc.
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