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Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices [Elektronski vir]Paradiž, Eva ...Tight control of beta cell stimulus-secretion coupling is crucial for maintaining homeostasis of energy-rich nutrients. While glucose serves as a primary regulator of this process, incretins augment ... beta cell function, partly by enhancing cytosolic [Ca2+] dynamics. However, the details of how precisely they affect beta cell recruitment during activation, their active time, and functional connectivity during plateau activity, and how they influence beta cell deactivation remain to be described. Performing functional multicellular Ca2+ imaging in acute mouse pancreas tissue slices enabled us to systematically assess the effects of the GLP-1 receptor agonist exendin-4 (Ex-4) simultaneously in many coupled beta cells with high resolution. In otherwise substimulatory glucose, Ex-4 was able to recruit approximately a quarter of beta cells into an active state. Costimulation with Ex-4 and stimulatory glucose shortened the activation delays and accelerated beta cell activation dynamics. More specifically, active time increased faster, and the time required to reach half-maximal activation was effectively halved in the presence of Ex-4. Moreover, the active time and regularity of [Ca2+]IC oscillations increased, especially during the first part of beta cell response. In contrast, subsequent addition of Ex-4 to already active cells did not significantly enhance beta cell activity. Network analyses further confirmed increased connectivity during activation and activity in the presence of Ex-4, with hub cell roles remaining rather stable in both control experiments and experiments with Ex-4. Interestingly, Ex-4 demonstrated a biphasic effect on deactivation, slightly prolonging beta cell activity at physiological concentrations and shortening deactivation delays at supraphysiological concentrations. In sum, costimulation by Ex-4 and glucose increases [Ca2+]IC during beta cell activation and activity, indicating that the effect of incretins may, to an important extent, be explained by enhanced [Ca2+]IC signals. During deactivation, previous incretin stimulation does not critically prolong cellular activity, which corroborates their low risk of hypoglycemia.Source: Frontiers in endocrinology [Elektronski vir]. - ISSN 1664-2392 (Vol. 14, Jan. 2024, str. 1-17)Type of material - e-articlePublish date - 2024Language - englishCOBISS.SI-ID - 181259011
Author
Paradiž, Eva |
Kerčmar, Jasmina |
Križančić Bombek, Lidija |
Pohorec, Viljem |
Skelin, Maša |
Rupnik, Marjan |
Gosak, Marko, 1982- |
Dolenšek, Jurij |
Stožer, Andraž
Topics
pancreas |
tissue slice |
beta cell |
calcium imaging |
exendin-4 |
incretin effect |
connectivity
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Author | Paradiž, Eva ... |
Title | Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices [Elektronski vir] |
Publication date | 2024-01-16 |
COBISS.SI-ID | 181259011 |
Publication version in repository | Postprint, author's finally reviewed version, accepted for publication |
Publication licence | Creative Commons Attribution 4.0 International |
Embargo | Unidentified |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
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Celične in tkivne mreže | P3-0396-2019 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Infrastrukturna dejavnost Univerze v Mariboru | I0-0029-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Vloga cikličnega adenozin monofosfata v normalni fiziologiji celic beta in med razvojem sladkorne bolezni tipa 2 | J3-9289-2018 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Pomen povezav med eksokrinim in endokrinim delom trebušne slinavke v zdravju in bolezni | N3-0170-2021 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Nevronski procesi, na katerih temelji socialna regulacija čustev in bolečine | J3-2525-2020 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Analiza kolektivne celične aktivnosti v normalnih in diabetičnih pankreatičnih otočkih s principi večplastnih mrež | J3-3077-2021 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Celice beta med razvojem in remisijo z dieto povzročene sladkorne bolezni | N3-0133-2020 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
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Costs of publication
Cost type | Total cost | Payments |
---|---|---|
APC – Article Processing Charge | 3627.11 € |
3627.11 € : Univerza v Mariboru, Medicinska fakulteta |
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DRS, in which the journal is indexed
Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Paradiž, Eva | 50674 |
Kerčmar, Jasmina | 32334 |
Križančić Bombek, Lidija | 24423 |
Pohorec, Viljem | 39524 |
Skelin, Maša | 29565 |
Rupnik, Marjan | 12266 |
Gosak, Marko, 1982- | 28405 |
Dolenšek, Jurij | 23415 |
Stožer, Andraž | 32132 |
Source: Personal bibliographies
and: SICRIS
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