20.500.12556/DKUM-65375 Modeliranje in senzitivnostna analiza heterogene populacije pankreasnih celic beta Modeling and sensitivity analysis of a heterogeneous population of pancreatic beta cells V delu se osredotočimo na modeliranje signalizacije v pankreasnih celicah beta. Te endokrine celice se nahajajo v Langerhansovih otočkih trebušne slinavke in so ključne pri uravnavi hormonskega ravnovesja v telesu. Njihova glavna naloga je izločanje hormona inzulina, ki je tesno povezana z dinamiko kalcijevih ionov. Le-ta je v celicah beta odvisna od glukoze in je sestavljena iz različnih oscilatornih podsistemov, in sicer glikolitičnega, mitohondrijskega in električno-kalcijevega. Zaradi kompleksnosti tega sistema se pri njegovem preučevanju poslužimo modeliranja in simulacij, ki nadgradijo eksperimentalne ugotovitve in omogočijo globlji vpogled v delovanje. Najprej smo preučevali celosten model ene celice in opravili senzitivnostno analizo modela, na podlagi katere smo razbrali ključne parametre in regulacijske procese, ki krojijo celično dinamiko in sekrecijo inzulina. V nadaljevanju smo izdelali večcelični mrežni model celic beta, ki vključuje tudi medcelično električno sklopitev preko presledkovnih stikov. V ta model smo vpeljali tako heterogenost celic kakor tudi heterogenost stičnih prevodnosti in na takšen način dobili dobro skladnost med rezultati simulacij in eksperimentov. The thesis focuses on the modeling of signaling pathways in pancreatic beta cells. These endocrine cells are located in the islets of Langerhans of the pancreas and are the key to maintaining hormonal balance in the body. Their main task is the secretion of hormone insulin, which is closely linked to the dynamics of calcium ions. The dynamics of calcium ions in the beta cells depends on the glucose and is composed of different oscillatory subsystems, namely glycolytic, mitochondrial and the electric-calcium compartment. Because of the complexity of this system, we employed modeling and simulations to complement experimental findings, thus enabling a deeper insight into the cellular mechanisms. First, we studied the overall model of one cell and performed the sensitivity analysis of the model, from which we obtained the key parameters and control processes that shape the cellular dynamics and the secretion of insulin. Then we constructed a multicellular network model of beta cells, which also includes the intercellular electrical coupling via gap junctions. In this section we introduced both cellular heterogeneity, as well as heterogeneity of junctional conductivity. In this way we obtained a good consistency between the results of simulations and experiments. Langerhansovi otočki celice beta kalcijeva signalizacija medcelična sklopitev geometrična mreža senzitivnostna analiza kalcijeve oscilacije sladkorna bolezen Islets of Langerhans beta cells calcium signaling intercellular coupling geometric network sensitivity analysis calcium oscillations diabetes mellitus true true false [M. Nassif] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2017-04-03 09:42:52 2017-05-08 10:25:06 2023-09-14 10:48:47 2019-07-11 15:16:15 2017 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577:519.8(043.2) 23067912 URN:SI:UM:DK:WSHXJWQO MAG_Nassif_Miha_2017.pdf MAG_Nassif_Miha_2017.pdf 1 D9EC17517C2786DAB7A384C2F807B6B0 1b9fc4765bb6a5ed3c84ae1e2a42629b352f7c5f2742a8353e66e53b209ad2b4 0d72bbf3-7c0e-11eb-bb7a-00155d0001ca https://dk.um.si/Dokument.php?lang=slv&id=110488 Fakulteta za naravoslovje in matematiko 0 0 0