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Title:Vplivi kalorične restrikcije na dinamiko kalcijevih oscilacij celic beta trebušne slinavke v mišjem modelu sladkorne bolezni tipa 2
Authors:ID Kopecky, Jan (Author)
ID Dolenšek, Jurij (Mentor) More about this mentor... New window
ID Stožer, Andraž (Comentor)
Files:.pdf MAG_Kopecky_Jan_2021.pdf (2,79 MB)
MD5: 018AB5B96F42A7176F82EF1CF4D6757E
PID: 20.500.12556/dkum/f60730e9-3eb1-4ee8-9722-e419ead50a7f
 
Language:Slovenian
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:FNM - Faculty of Natural Sciences and Mathematics
Abstract:Sladkorna bolezen tipa 2 (SB2) je zapletena presnovna bolezen, za katero je značilna izguba funkcije celic beta v Langerhansovih otočkih. Ker predstavlja SB2 vedno večji globalni problem, je potrebno poglobiti naše znanje in iskati nove metode ter terapevtske načine, kako jo zajeziti. Dinamika znotrajcelične koncentracije kalcijevih ionov v celicah beta igra ključno vlogo pri sklopitvi med stimulusom in sekrecijo ter je tesno povezana z izločanjem inzulina. Zato je razumevanje tega procesa ključno za vpogled v mehanizme, prisotne pri SB2. Kratkotrajna kalorična restrikcija vodi do remisije SB2. Da bi razjasnili naše razumevanje o vplivu kalorične restrikcije na celice beta in mehanizma remisije SB2, smo v magistrski nalogi raziskovali vpliv kalorične restrikcije na dinamiko kalcijevih oscilacij v celicah beta. Poskuse smo izvedli na samcih miši linije C57BL/6J, ki smo jih razdelili v tri skupine. Ena skupina miši je prejemala kontrolno prehrano (CD), druga zahodno prehrano (WD), tretjo pa smo po določenem času hranjenja z WD izpostavili kalorični restrikciji (RCD). Pri WD miših se je pojavila delno kompenzirana SB2, inzulinska rezistenca in hiperglikemije na tešče. Dinamiko znotrajcelične koncentracije kalcijevih ionov smo snemali s konfokalnim mikroskopom na akutnih tkivnih rezinah trebušne slinavke ob stimuliranju z različnimi koncentracijami glukoze. Zaznali smo značilen vzorec kalcijevih oscilacij celic beta. V svoji magistrski nalogi sem podrobneje preučeval plato fazo oscilacij znotrajcelične koncentracije kalcijevega iona, natančneje aktivni čas, frekvence in dolžine oscilacij. Celice beta WD miši so delno kompenzirale inzulinsko rezistenco s povečano aktivnostjo, ki se je izrazila predvsem v aktivnem času oscilacij. Ugotovili smo, da je kalorična restrikcija signifikantno znižala aktivni čas in dolžino oscilacij. Ko smo preučevali vpliv koncentracije glukoze na dinamiko kalcijevih oscilacij, smo pri vseh skupinah zasledili trend naraščanja aktivnega časa in dolžine oscilacij ob naraščanju koncentracije glukoze. Pri frekvenci oscilacij nismo zaznali jasnega vzorca ne med tretmaji in ne ob večanju koncentracije glukoze. Kratkotrajna kalorična restrikcija je izboljšala inzulinsko občutljivost, povzročila normoglikemijo in povrnila aktivnost celic beta na raven CD miši. Rezultati nam nudijo boljši vpogled v mehanizme SB2 in nudijo dobro platformo za študij SB2 na živalskih modelih.
Keywords:celice beta, kalcijev ion, kalorična restrikcija, Langerhansov otoček, zahodna dieta, inzulin
Place of publishing:Maribor
Publisher:[J. Kopecky]
Year of publishing:2021
PID:20.500.12556/DKUM-80289 New window
UDC:577:613.2(043.2)
COBISS.SI-ID:79234819 New window
Publication date in DKUM:24.12.2021
Views:1357
Downloads:113
Metadata:XML DC-XML DC-RDF
Categories:FNM
:
KOPECKY, Jan, 2021, Vplivi kalorične restrikcije na  dinamiko kalcijevih oscilacij  celic beta trebušne slinavke v  mišjem modelu sladkorne  bolezni tipa 2 [online]. Master’s thesis. Maribor : J. Kopecky. [Accessed 17 April 2025]. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=80289
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Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:06.09.2021

Secondary language

Language:English
Title:Effects of caloric restriction on calcium dynamic of pancreas ß cells in a mouse model of type 2 diabetes effects of caloric restriction on calcium dynamic of pancreas ß cells in a mouse model of type 2 diabetes
Abstract:Type 2 diabetes mellitus (T2DM) is a complex metabolic disease, characterized by the loss of beta cell function in the islets of Langerhans. As rising global incidence of T2DM poses an ever-increasing global problem, necessitating to deepen our knowledge and look for new methods and therapeutics to curb its spread. Calcium ion dynamics in beta cells play a key role in the coupling between stimulus and secretion which is closely related to insulin secretion. Therefore, understanding this process is crucial for a better insight into the mechanisms present in T2DM. Short-term caloric restriction is known to cause remission of T2DM. In order to clarify our understanding of the effect of caloric restriction on beta cells and underlying mechanism behind T2DM remission, we tried to deepen our knowledge of the effect of caloric restriction on the dynamics of calcium oscillations. We performed our experiments on male C57BL/6J mice, which were divided into three groups according to diet type and regiment. One group of mice (healthy control mice) was fed control diet (CD), another Western diet (WD), and a third was submitted to caloric restriction (RCD) after a period of having recived WD. In WD mice, partial compensation of T2DM occurred in the form of insulin resistance and fasting hyperglycemia. Calcium ion dynamics were recorded using a confocal microscope on acute pancreatic tissue slices while being stimulated with different glucose concentrations. We detected a pattern of calcium oscillations that was characteristic for beta cells in all three experimental groups. The focus of this study was directed towards the plateau phase of citoplasmic Ca2+ oscillations. We measured the active time, frequency, and duration of oscillations of individual beta cells. Beta cells in WD fed mice partially compensated for insulin resistance with increased activity, which expressed itself mainly in active time. We found that caloric restriction significantly reduced the active time and duration of Ca2+ oscilations in WD fed mice to a degree, comparable to CD mice. When studying the influence of glucose concentration, we observed a trend of increase in active time and duration of oscillations with respect to increasing glucose concentration in all three groups. We did not detect a clear pattern in oscillation frequency throughout treatments or with increasing glucose concentration. Short-term caloric restriction improved insulin sensitivity, resulted in normoglycemia, and restored beta cell activity to the level found in CD fed mice. Our findings further elucidated the impact of caloric restriction on T2DM and provide a strong platform for studying T2DM on animal models.
Keywords:Beta cells, calcium ion, caloric restriction, Langerhans islet, Western diet, insulin


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