| Naslov: | Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic ▫$\alpha$▫-cells |
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| Avtorji: | ID Grubelnik, Vladimir (Avtor)
ID Markovič, Rene (Avtor)
ID Lipovšek Delakorda, Saška (Avtor)
ID Leitinger, Gerd (Avtor)
ID Gosak, Marko (Avtor)
ID Dolenšek, Jurij (Avtor)
ID Valladolid-Acebes, Ismael (Avtor)
ID Berggren, Per-Olof (Avtor)
ID Stožer, Andraž (Avtor)
ID Perc, Matjaž (Avtor)
ID Marhl, Marko (Avtor) |
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| Datoteke: |  RAZ_Grubelnik_Vladimir_2020.pdf (1,60 MB)
MD5: 35737F9D5ADEB2C5ECF1A5440AB73BA3
 https://doi.org/10.1098/rsos.191171
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| Jezik: | Angleški jezik |
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| Vrsta gradiva: | Članek v reviji |
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| Tipologija: | 1.01 - Izvirni znanstveni članek |
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| Organizacija: | FERI - Fakulteta za elektrotehniko, računalništvo in informatiko
FNM - Fakulteta za naravoslovje in matematiko
MF - Medicinska fakulteta
PEF - Pedagoška fakulteta
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| Opis: | 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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| Ključne besede: | diabetes, pancreatic alpha cells, glucagon, mitochondrial dysfunction, free fatty acid |
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| Status publikacije: | Objavljeno |
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| Verzija publikacije: | Objavljena publikacija |
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| Poslano v recenzijo: | 15.07.2019 |
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| Datum sprejetja članka: | 16.12.2019 |
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| Datum objave: | 22.01.2020 |
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| Založnik: | Royal Society Publishing |
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| Leto izida: | 2020 |
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| Št. strani: | str. 1-17 |
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| Številčenje: | Vol. 7, iss. 1 |
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| PID: | 20.500.12556/DKUM-90130  |
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| UDK: | 616.379 |
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| COBISS.SI-ID: | 25073672 |
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| DOI: | 10.1098/rsos.191171 |
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| ISSN pri članku: | 2054-5703 |
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| Datum objave v DKUM: | 03.09.2024 |
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| Število ogledov: | 49 |
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| Število prenosov: | 4 |
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| Metapodatki: |    |
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| Področja: | Ostalo
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