| Title: | The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks |
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| Authors: | ID Skelin, Maša (Author)
ID Dolenšek, Jurij (Author)
ID Križančić Bombek, Lidija (Author)
ID Pohorec, Viljem (Author)
ID Gosak, Marko (Author)
ID Rupnik, Marjan (Author)
ID Stožer, Andraž (Author) |
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| Files: |  Klemen-2023-The_effect_of_forskolin_and_the_ro.pdf (12,03 MB)
MD5: 5FA1E7D4A63AC94990D869610F1D7311
 https://doi.org/10.3389/fendo.2023.1225486
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| Language: | English |
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| Work type: | Scientific work |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | MF - Faculty of Medicine
FNM - Faculty of Natural Sciences and Mathematics
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| Abstract: | Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. Cyclic adenosine monophosphate (cAMP) amplifies stimulus-secretion coupling via protein kinase A and guanine nucleotide exchange protein 2 (Epac2A). With the present research, we aimed to clarify the influence of cAMP-elevating diterpene forskolin on cytoplasmic calcium dynamics and intercellular network activity, which are two of the crucial elements of normal beta cell stimulus-secretion coupling, and the role of Epac2A under normal and stimulated conditions. To this end, we performed functional multicellular calcium imaging of beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Forskolin evoked calcium signals in otherwise substimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and stimulation with forskolin increased the active time via an increase in oscillation frequency and a decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of stimulation with forskolin in preventing a decline in beta cell functional connectivity with time. Finally, stimulation with forskolin prolonged beta cell activity during deactivation, especially in Epac2A knock-out mice. |
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| Keywords: | pancreas, tissue slices, beta cells, calcium imaging, amplifying pathway, forskolin, Epac2A KO, intercellular network |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 19.05.2023 |
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| Article acceptance date: | 08.08.2023 |
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| Publication date: | 28.08.2023 |
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| Publisher: | Frontiers Research Foundation |
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| Year of publishing: | 2023 |
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| Number of pages: | Str. 1-14 |
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| Numbering: | Letn. 14, Št. članka 1225486 |
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| PID: | 20.500.12556/DKUM-88814  |
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| UDC: | 612.349.7 |
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| ISSN on article: | 1664-2392 |
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| COBISS.SI-ID: | 163143427 |
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| DOI: | 10.3389/fendo.2023.1225486 |
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| Publication date in DKUM: | 27.05.2024 |
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| Views: | 324 |
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| Downloads: | 30 |
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| Metadata: |    |
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| Categories: | Misc.
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