Vladimir Grubelnik (Author), Rene Markovič (Author), Saška Lipovšek Delakorda (Author), Gerd Leitinger (Author), Marko Gosak (Author), Jurij Dolenšek (Author), Ismael Valladolid-Acebes (Author), Per-Olof Berggren (Author), Andraž Stožer (Author), Matjaž Perc (Author), Marko Marhl (Author)

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.

Keywords

diabetes;alfa celice;glukagon;mithondrijska disfunkcija;proste maščobne kisline;ne zaključna dela;pancreatic alpha cells;glucagon;mitochondrial dysfunction;free fatty acid;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UM FNM - Faculty of Natural Sciences and Mathematics
Publisher: Royal Society Publishing
UDC: 616.379
COBISS: 25073672 Link will open in a new window
ISSN: 2054-5703
Views: 17
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Other data

Secondary language: Slovenian
Secondary keywords: Sladkorna bolezen;
Type (COBISS): Article
Pages: str. 1-17
Volume: ǂVol. ǂ7
Issue: ǂiss. ǂ1
Chronology: 2020
DOI: 10.1098/rsos.191171
ID: 24893128