Vladimir Grubelnik (Avtor), Jan Zmazek (Avtor), Rene Markovič (Avtor), Marko Gosak (Avtor), Marko Marhl (Avtor)

Povzetek

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.

Ključne besede

endokrine celice trebušne slinavke;matematični modeli;mitohondrijska disfunkcija;celularna bioenergetika;diabetes;glukagon;inzulin;ne zaključna dela;pancreatic endocrine cells;mathematical model;mitochondrial dysfunction;cellular bioenergetics;glucagon;insulin;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UM FNM - Fakulteta za naravoslovje in matematiko
Založnik: MDPI
UDK: 616.379
COBISS: 43234819 Povezava se bo odprla v novem oknu
ISSN: 2075-1729
Št. ogledov: 47
Št. prenosov: 12
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;Matematični modeli;
Vrsta dela (COBISS): Znanstveno delo
Strani: str. 1-16
Letnik: ǂVol. ǂ10
Zvezek: ǂno. ǂ12
Čas izdaje: 2020
DOI: 10.3390/life10120348
ID: 24893142