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

Povzetek

Glucose metabolism plays a crucial role in modulating glucagon secretion in pancreatic alpha cells. However, the downstream effects of glucose metabolism and the activated signaling pathways influencing glucagon granule exocytosis are still obscure. We developed a computational alpha cell model, implementing metabolic pathways of glucose and free fatty acids (FFA) catabolism and an intrinsically activated cAMP signaling pathway. According to the model predictions, increased catabolic activity is able to suppress the cAMP signaling pathway, reducing exocytosis in a Ca2+ - dependent and Ca2+ independent manner. The effect is synergistic to the pathway involving ATPdependent closure of KATP channels and consequent reduction of Ca2+. We analyze the contribution of each pathway to glucagon secretion and show that both play decisive roles, providing a kind of "secure double switch". The cAMP-driven signaling switch plays a dominant role, while the ATP-driven metabolic switch is less favored. The ratio is approximately 60:40, according to the most recent experimental evidence.

Ključne besede

pancreatic alpha cell;glucagon;cAMP;mathematical model;diabetes;cellular bioenergetics;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UM FNM - Fakulteta za naravoslovje in matematiko
Založnik: MDPI
UDK: 612.349.7
COBISS: 59694339 Povezava se bo odprla v novem oknu
ISSN: 2073-4409
Št. ogledov: 16
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: Angleški jezik
Sekundarne ključne besede: Matematični modeli;Biofizika;Sladkorna bolezen;
Vrsta dela (COBISS): Članek v reviji
Strani: 22 str.
Letnik: ǂVol. ǂ10
Zvezek: ǂiss. ǂ4
Čas izdaje: 2021
DOI: 10.3390/cells10040896
ID: 24063084