Role of cAMP in double switch of glucagon secretion

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

Abstract

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.

Keywords

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

Data

Language:	English
Year of publishing:	2021
Typology:	1.01 - Original Scientific Article
Organization:	UM FNM - Faculty of Natural Sciences and Mathematics
Publisher:	MDPI
UDC:	612.349.7
COBISS:	59694339
ISSN:	2073-4409
Views:	16
Downloads:	0
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary keywords:	Matematični modeli;Biofizika;Sladkorna bolezen;
Type (COBISS):	Article
Pages:	22 str.
Volume:	ǂVol. ǂ10
Issue:	ǂiss. ǂ4
Chronology:	2021
DOI:	10.3390/cells10040896
ID:	24063084