| | SLO | ENG | Cookies and privacy

Bigger font | Smaller font

Show document Help

Title:Vloga receptorjev za inozitol (1,4,5) trisfosfat v celicah beta Langerhansovih otočkov trebušne slinavke
Authors:ID Murko, Nastja (Author)
ID Slak Rupnik, Marjan (Mentor) More about this mentor... New window
ID Stožer, Andraž (Comentor)
Files:.pdf DOK_Murko_Nastja_2026.pdf (3,35 MB)
MD5: 8E03208027472A114DCA559C3EB39803
 
Language:Slovenian
Work type:Dissertation
Typology:2.08 - Doctoral Dissertation
Organization:MF - Faculty of Medicine
Abstract:Znotrajcelična Ca²⁺ signalizacija predstavlja osrednji regulator izločanja hormona inzulina iz celic beta in s tem presnovne homeostaze. Kolikšno vlogo pri tem igra od IP₃-posredovana mobilizacija Ca²⁺, še ni v celoti pojasnjeno. V tej doktorski nalogi smo z uporabo svežih tkivnih rezin trebušne slinavke in konfokalne mikroskopije preučevali, kako aktivacija Gq/IP₃ signalne poti oblikuje prostorsko-časovno dinamiko Ca²⁺ signalov v endokrinih celicah pankreasa ter kako se ta signalizacija prepleta z drugimi signalnimi potmi. Pokazali smo, da je IP₃-odvisna signalizacija izrazito odvisna od izhodiščnega funkcionalnega stanja celic in celičnega tipa. Z uporabo hormona arginin-vazopresina kot modelnega agonista Gq-sklopljenih receptorjev smo ugotovili, da le-ta pri nizkih koncentracijah glukoze selektivno aktivira celice α, medtem ko celice β ostanejo neaktivne. Pri koncentracijah glukoze, ki že stimulirajo celice β, arginin-vazopresin modulira Ca²⁺ dinamiko v teh celicah pri čemer učinki sledijo značilni zvonasti koncentracijski odvisnosti. Dodatno smo pokazali, da tudi acetilholin, ki podobno deluje preko Gq- sklopljenih receptorjev, pri fizioloških koncentracijah modulira Ca²⁺ aktivnost v celicah β, medtem ko adrenalin pri fizioloških koncentracijah preko Gi- sklopljene signalne poti zavira njihovo aktivnost. Naši rezultati opredeljujejo IP₃ signalizacijo kot ključno integracijsko vozlišče, ki v interakciji s cAMP-odvisnimi mehanizmi določa celično-specifične Ca²⁺ odzive ter usklajuje delovanje endokrinega dela pankreasa. Ti izsledki pomembno prispevajo k razumevanju mehanizmov sklopitve dražljaj–izločanje in potencialnih mehanizmov, ki vodijo v njihovo porušenje in sladkorno bolezen.
Keywords:IP3 signalizacija, celice β, dinamika Ca2+, konfokalna mikroskopija, tkivne rezine trebušne slinavke
Place of publishing:Maribor
Publisher:[N. Murko]
Year of publishing:2026
PID:20.500.12556/DKUM-97655 New window
UDC:577.121+612.346/.349.8:616-092.18(043.3)
COBISS.SI-ID:285944835 New window
Publication date in DKUM:06.08.2026
Views:243
Downloads:15
Metadata:XML DC-XML DC-RDF
Categories:MF
:
Copy citation
  
Average score:(0 votes)
Your score:Voting is allowed only for logged in users.
Share:Bookmark and Share



Hover the mouse pointer over a document title to show the abstract or click on the title to get all document metadata.

Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:30.03.2026

Secondary language

Language:English
Title:The Role of Inositol (1,4,5)-Trisphosphate Receptors in Beta Cells of the Pancreatic Islets of Langerhans
Abstract:Intracellular Ca²⁺ signaling is a central regulator of insulin secretion and metabolic homeostasis; however, the contribution of IP₃-mediated Ca²⁺ mobilization to signal integration in intact islet tissue remains incompletely understood. In this doctoral thesis, we used acute pancreatic tissue slices combined with confocal microscopy to investigate how activation of the Gq/IP₃ signaling pathway shapes the spatiotemporal dynamics of Ca²⁺ signals in endocrine pancreatic cells and how this pathway interacts with other regulatory mechanisms. We demonstrate that IP₃-dependent signaling is strongly dependent on the functional state of the cells and is cell-type specific. Using arginine vasopressin as a model Gq-coupled agonist, we show that at low glucose concentrations arginin vasopressin selectively activates α cells, while β cells remain inactive. At stimulatory glucose levels, arginin vazopresin modulates Ca²⁺ dynamics in β cells, with effects following a characteristic bell-shaped concentration–response relationship. In addition, we show that acetylcholine, at physiologically relevant concentrations, modulates Ca²⁺ activity in β cells via the Gq/IP₃ signaling pathway, whereas adrenaline, also at physiologically relevant concentrations, inhibits β-cell activity via Gi signaling. Our results identify IP₃ signaling as a key integrative node that, in interaction with cAMP- dependent mechanisms, governs cell-specific Ca²⁺ responses and coordinates endocrine pancreatic function. These findings provide important insight into stimulus–secretion coupling and its dysregulation in diabetes.
Keywords:IP3 signaling, beta cells, Ca2+ dynamics, confocal microscopy, pancreatic tissue slices


Comments

Leave comment

You must log in to leave a comment.

Comments (0)
0 - 0 / 0
 
There are no comments!

Back
Logos of partners University of Maribor University of Ljubljana University of Primorska University of Nova Gorica