| Title: | Role of cAMP in double switch of glucagon secretion |
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| Authors: | ID Zmazek, Jan (Author)
ID Grubelnik, Vladimir (Author)
ID Markovič, Rene (Author)
ID Marhl, Marko (Author) |
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| Files: |  https://www.mdpi.com/2073-4409/10/4/896
 RAZ_Zmazek_Jan_2021.pdf (2,58 MB)
MD5: CA82892AE60A59840969139C04569A1B
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| Language: | English |
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| Work type: | Article |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | FNM - Faculty of Natural Sciences and Mathematics
FERI - Faculty of Electrical Engineering and Computer Science
PEF - Faculty of Education
MF - Faculty of Medicine
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| 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. |
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| Keywords: | pancreatic alpha cell, glucagon, cAMP, mathematical model, diabetes, cellular bioenergetics |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 15.03.2021 |
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| Article acceptance date: | 12.04.2021 |
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| Publication date: | 14.04.2021 |
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| Publisher: | MDPI |
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| Year of publishing: | 2021 |
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| Number of pages: | 22 str. |
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| Numbering: | Vol. 10, iss. 4 |
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| PID: | 20.500.12556/DKUM-89006  |
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| UDC: | 612.349.7 |
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| ISSN on article: | 2073-4409 |
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| COBISS.SI-ID: | 59694339 |
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| DOI: | 10.3390/cells10040896 |
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| Publication date in DKUM: | 06.06.2024 |
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| Views: | 272 |
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| Downloads: | 20 |
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| Metadata: |    |
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| Categories: | Misc.
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