| Title: | Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic ▫$\alpha$▫-cells |
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| Authors: | ID Grubelnik, Vladimir (Author)
ID Markovič, Rene (Author)
ID Lipovšek Delakorda, Saška (Author)
ID Leitinger, Gerd (Author)
ID Gosak, Marko (Author)
ID Dolenšek, Jurij (Author)
ID Valladolid-Acebes, Ismael (Author)
ID Berggren, Per-Olof (Author)
ID Stožer, Andraž (Author)
ID Perc, Matjaž (Author)
ID Marhl, Marko (Author) |
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| Files: |  RAZ_Grubelnik_Vladimir_2020.pdf (1,60 MB)
MD5: 35737F9D5ADEB2C5ECF1A5440AB73BA3
 https://doi.org/10.1098/rsos.191171
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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: | Type 2 diabetes mellitus (T2DM) has been associated with insulin resistance and the failure of β-cells to produce and secrete enough insulin as the disease progresses. However, clinical treatments based solely on insulin secretion and action have had limited success. The focus is therefore shifting towards α-cells, in particular to the dysregulated secretion of glucagon. Our qualitative electron-microscopy-based observations gave an indication that mitochondria in α-cells are altered in Western-diet-induced T2DM. In particular, α-cells extracted from mouse pancreatic tissue showed a lower density of mitochondria, a less expressed matrix and a lower number of
cristae. These deformities in mitochondrial ultrastructure imply a decreased efficiency in mitochondrial ATP production, which prompted us to theoretically explore and clarify one of the most challenging problems associated with T2DM, namely the lack of glucagon secretion in hypoglycaemia and its oversecretion at high blood glucose concentrations. To this purpose, we constructed a novel computational model that links α-cell metabolism with their electrical activity and glucagon secretion. Our results show that defective mitochondrial metabolism in α-cells can
account for dysregulated glucagon secretion in T2DM, thus improving our understanding of T2DM pathophysiology and indicating possibilities for new clinical treatments.
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| Keywords: | diabetes, pancreatic alpha cells, glucagon, mitochondrial dysfunction, free fatty acid |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 15.07.2019 |
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| Article acceptance date: | 16.12.2019 |
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| Publication date: | 22.01.2020 |
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| Publisher: | Royal Society Publishing |
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| Year of publishing: | 2020 |
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| Number of pages: | str. 1-17 |
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| Numbering: | Vol. 7, iss. 1 |
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| PID: | 20.500.12556/DKUM-90130  |
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| UDC: | 616.379 |
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| ISSN on article: | 2054-5703 |
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| COBISS.SI-ID: | 25073672 |
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| DOI: | 10.1098/rsos.191171 |
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| Publication date in DKUM: | 03.09.2024 |
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| Views: | 231 |
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| Downloads: | 18 |
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| Metadata: |    |
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| Categories: | Misc.
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