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Title:Analiza širjenja kalcijevih valov v tridimenzionalnih tkivih: od teorije do eksperimenta
Authors:Zakelšek, Darko (Author)
Gosak, Marko (Mentor) More about this mentor... New window
Dolenšek, Jurij (Co-mentor)
Files:.pdf MAG_Zakelsek_Darko_2019.pdf (3,14 MB)
 
Language:Slovenian
Work type:Master's thesis/paper (mb22)
Typology:2.09 - Master's Thesis
Organization:FNM - Faculty of Natural Sciences and Mathematics
Abstract:V nalogi smo preučevali razširjanje kalcijevih valov med celicami beta v Langerhansovih otočkih. Ti valovi so pomemben sinhronizacijski mehanizem in izvirajo iz oscilatorne dinamike koncentracije kalcijevih ionov znotraj pankreasnih celic beta, do katere pride, ko so celice stimulirane z glukozo. V nalogi smo najprej pojasnili fiziološke mehanizme, ki vodijo do oscilirajoče kalcijeve signalizacije in izpostavili pomembnost sinhronega delovanja celic beta. Znano namreč je, da ob razvoju sladkorne bolezni tipa 2, celice postanejo manj usklajene, vzorci izločanja inzulina pa so zaradi tega nepravilni. Organizacijski principi proženja kalcijevih valov niso povsem znani, eksperimentalni podatki pa so omejeni, saj lahko opazujemo le eno dvodimenzionalno presečno ravnino tkiva. V magistrskem delu smo se problematike lotili postopno. Najprej smo teoretično obravnavali prenos krožnih valov po tkivu in izpeljali, kako lahko določimo izvore valov le na podlagi poznavanja profila aktivacij v eni presečni ravnini. V nadaljevanju smo izdelali numerični model, s katerim smo po eni strani preverili naše teoretične napovedi, po drugi strani pa tudi preučili, kako na širjenje valov vplivajo realni fiziološki dejavniki, kot sta heterogenost celic in stohastična narava celične signalizacije. Izkazalo se je, da lahko z našim modelom precej natančno določimo izvore valov. V zadnjem delu smo naš teoretični konstrukt uporabili še za analizo eksperimentalnih meritev širjenja valov po tkivni rezini in določili izvore kalcijevih valov ter ocenili njihovo hitrost. Rezultati naloge pomenijo korak naprej pri razumevanju narave kalcijeve signalizacije in funkcionalne organiziranosti celic beta v Langerhansovih otočkih.
Keywords:Langerhansovi otočki, celice beta, kalcijevi valovi, medcelična sklopitev, numerično modeliranje.
Year of publishing:2019
Publisher:[D. Zakelšek]
Source:Maribor
UDC:577(043.2)
COBISS_ID:24864520 Link is opened in a new window
NUK URN:URN:SI:UM:DK:0QUEMC6J
License:CC BY-NC-ND 4.0
This work is available under this license: Creative Commons Attribution Non-Commercial No Derivatives 4.0 International
Views:58
Downloads:5
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Categories:FNM
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Secondary language

Language:English
Title:Analysis of calcium wave propagation in three-dimensional tissues: from theory to experiment
Abstract:In the master thesis, we have examined the propagation of calcium waves between beta cells in the islets of Langerhans. These waves represent an important synchronization mechanism and originate from the oscillatory dynamics of calcium ions within the pancreatic beta cells, which is triggered by glucose stimulation. In the present work we have first explained the physiological mechanisms that are responsible for the oscillatory nature of calcium signalization and emphasized the importance of synchronous behaviour. Namely, during the development of type 2 diabetes, the cells become less coordinated and the insulin secretion patterns become impaired. The organizing principles of calcium wave initiation are incompletely understood and the experimental data is only limited, since it is possible to observe only a two-dimensional cross-section of the tissue. In the thesis we engaged with these issues in a stepwise manner. Firstly, we have theoretically examined the propagation of spherical waves in the tissue and derived how the initiator areas can be detected only by knowing the activation profiles in one cross-section. Then, we developed a numerical model which enabled us to verify our theoretical predictions and facilitated the investigation on how realistic physiological determinants, such as heterogeneity of cells and the stochastic nature of cellular signalization, affect the course of waves. It turned out that our model copes to detect the initiating areas rather precisely. Finally, we utilized our theoretical framework to analyse the experimental measurements of calcium wave propagation is tissue slices and determined the initiating regions and estimated the speed of wave propagation. Our results represent a step forward towards the understanding of calcium signalization and the functional organization of beta cells in islets of Langerhans.
Keywords:Islets of Langerhans, beta cells, calcium waves, intercellular coupling, numerical modelling.


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