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

Povzetek

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.

Ključne besede

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

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UM FNM - Fakulteta za naravoslovje in matematiko
Založnik: Royal Society Publishing
UDK: 616.379
COBISS: 25073672 Povezava se bo odprla v novem oknu
ISSN: 2054-5703
Št. ogledov: 17
Št. prenosov: 0
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Sladkorna bolezen;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-17
Letnik: ǂVol. ǂ7
Zvezek: ǂiss. ǂ1
Čas izdaje: 2020
DOI: 10.1098/rsos.191171
ID: 24893128