Приказ основних података о дисертацији
Uloga galektina-3 u patofiziologiji ß ćelija pankreasa
The role of galectin-3 in pancreatic ß cells pathophysiology
| dc.contributor.advisor | Jovičić, Nemanja | |
| dc.contributor.other | Lalić, Nebojša M. | |
| dc.contributor.other | Lukić, Miodrag L. | |
| dc.contributor.other | Živančević Simonović, Snežana | |
| dc.contributor.other | Đukić, Aleksandar | |
| dc.creator | Petrović, Ivica | |
| dc.date.accessioned | 2021-04-19T09:37:30Z | |
| dc.date.available | 2021-04-19T09:37:30Z | |
| dc.date.issued | 2021-01-18 | |
| dc.identifier.uri | http://eteze.kg.ac.rs/application/showtheses?thesesId=7896 | |
| dc.identifier.uri | https://fedorakg.kg.ac.rs/fedora/get/o:1312/bdef:Content/download | |
| dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/18238 | |
| dc.description | Uvod: Šećerna bolest predstavlja sve značajniji zdravstveni problem u svetu. U patogenezi tipa 1 šećerne bolesti centralno mesto zauzima autoimunsko zapaljenje pankreasnih ostrvaca koje vodi apsolutnom nedostatku insulina. Centralno mesto u patogenezi tipa 2 šećerne bolesti, zauzima razvoj gojaznosti sa pojavom rezistencije perifernih tkiva na insulin i posledičnim povećanjem stvaranja insulina. Povećani zahtevi za produkciju insulina stimulišu, ali i opterećuju β ćelije, što postepeno vodi njihovom oštećenju koje je praćeno smanjenim stvaranjem insulina, pojavom hiperglikemije i razvojem tipa 2 šećerne bolesti. Dosadašnja istraživanja u kojima su korišćeni galektin-3 deficijentni miševi, pokazala su prozapaljensku ulogu galektina-3 u razvoju tipa 1 šećerne bolesti, dok su rezultati ispitivanja uloge ovog molekula u patogenezi tipa 2 šećerne bolesti kontradiktorni. Do sada nema podataka o efektu selektivno pojačane ekspresije galektina-3 u β ćelijama na patogenezu šećerne bolesti. Cilj: Ispitati efekat pojačane ekspresije galektina-3 u β ćelijama na patogenezu šećerne bolesti. Materijal i metode: Eksperimentalnim životinjama, C57Bl/6 miševima divljeg soja i miševima sa transgeno pojačanom ekspresijom galektina-3 u β ćelijama, tip 1 šećerne bolesti je indukovan primenom streptozotocina u pet malih doza od 40mg/kg, dok je tip 2 šećerne bolesti indukovan korišćenjem hrane bogate mastima (engl. high fat diet, HFD, 60% kalorija porekla iz masnih kiselina) tokom 16 nedelja. U in vitro eksperimentima korišćena su izolovana pankreasna ostrvca koja su tretirana metaboličkim noksama nakon čega je analizirano preživljavanje β ćelija kao i oskidativni potencijal tretiranih β ćelija. U eksperimenatlnom modelu tipa 1 šećerne bolesti, aplikovan je interleukin 33 u 4 doze od 12-18 dana modela. Rezultati: U eksperimentalnom modelu tipa 1 šećerne bolesti transgeno pojačana ekspresija galektina-3 u β ćelijama deluje protektivno, na indukciju bolesti upotrebom niskih uzastopnih doza streptozotocina. Tretiranje transgenih miševa interleukinom 33 dodatno ublažava razvoj hiperglikemija. U eksperimentalnom modelu tipa 2 šećerne bolesti trasngeno pojačana ekspresija galektina-3 u β ćelijama deluje prozapaljenski pospešujući oštećenje β ćelija nakon ishrane bogate mastima. In vitro rezultati ukazuju na prooksidantni efekat pojačane ekspresije galektina-3 u β ćelijama, dok rezultati nakon stimulacije metaboličkim i inflamatornim noksama pokazuju značajan prozapaljenski efekat pojačane ekspresije galektina-3 u β ćelijama. Zaključak: Rezultati pokazuju da efekat pojačane ekspresije galektina-3 u β ćelijama može biti dvojak, od protektivnog do prozapaljenskog, u zavisnosti od nokse koja deluje na β ćelije i mehanizma kojim noksa dovodo do oštećenja β ćelije. Transgeno pojačana ekspresija galektina-3 u β ćelijama i primena interleukina 33 nakon pojave hiperglikemije imaju terapijski efekat i sprečavaju razvoj šećerne bolesti. | sr |
| dc.description | Introduction: Diabetes is a serious and emerging health problem around the world. The central place in type 1 diabetes pathogenesis belongs to autoimmune inflammation of the pancreatic islets, which leads to an absolute lack of insulin. In type 2 diabetespathogenesis, central role belongs to development of obesity, metainflammation and appearance of peripheral tissue resistance to insulin with the consequent increase in insulin production. β cells, burdened with increased demands, cannot withstand the new condition for a long time, which gradually leads to their damage, accompanied by reduced insulin production, hyperglycemia and type 2 diabetes onset. Previous studies which used galectin-3 deficient mice shown its proinflammatory role in the development of type 1 diabetes, while the results of examining the role of this molecule in the pathogenesis of type 2 diabetes are contradictory. There are no data in the literature about the effect of selectively enhanced galectin-3 expression in β cells on the pathogenesis of diabetes. Aim: The aim of the research project was to delineate the role of galectin-3, expressed on β cells, in the pathogenesis of diabetes. Material and methods: Type 1 diabetes was induced by multiple low doses of streptozotocin (40 mg/kg) in C57Bl/6 wild type mice and mice with transgenically enhanced galectin-3 expression in β cells. Type 2 diabetes was induced by use of high-fat diet (HFD, 60% calories from fat) for 16 weeks. In in vitro experiments, isolated islets were treated with metabolically harmful factors, after which the survival of β cells was investigated, as well as the oxidative potential of the treated β cells. In experimental model of type 1 diabetes, additional experimental groups were treated with interleukin 33 in 4 doses from 12 to 18 days. Results: In experimental model of type 1 diabetes, enhanced galectin-3 expression in β cells has a protective effect on disease induction. Interleukin 33 treatment further reduces the development of hyperglycemia in transgenic mice group. In experimental model of type 2 diabetes, transgenically enhanced galectin-3 in β cells has pro-inflammatory effect, accelerating β cell damage after 16 weeks of high fat diet. In vitro results indicated that transgenically enhanced galectin-3 expression in β cells has a prooxidant effect, while results after stimulation with metabolically and immune harmful factors showed a significant pro-inflammatory effect of enhanced galectin-3 in β cells. Conclusion: It seems that the effect of transgenically increased expression of galectin-3 in β cells can be twofold, from protective to pro-inflammatory. The end effect depends on the type of harmful factor acting on the β cells, as well as the pathways that leads to damage to the β cells. The therapeutic effect of interleukin 33, after the development of hyperglycemia, is significantly pronounced in mice with transgenically enhanced galectin-3 expression in β cells. | en |
| dc.format | application/pdf | |
| dc.language | sr | |
| dc.publisher | Универзитет у Крагујевцу, Факултет медицинских наука | |
| dc.rights | openAccess | en |
| dc.rights.uri | https://creativecommons.org/licenses/by-nd/4.0/ | |
| dc.source | Универзитет у Крагујевцу | sr |
| dc.subject | pojačana ekspresija galektina-3 | sr |
| dc.subject | enhanced expression of galectin-3 | en |
| dc.subject | oksidativni stres | sr |
| dc.subject | ishrana bogata mastima | sr |
| dc.subject | streptozotocin | sr |
| dc.subject | apoptoza β ćelija | sr |
| dc.subject | interleukin 33 | sr |
| dc.subject | terapija šećerne bolesti | sr |
| dc.subject | diabetes | en |
| dc.subject | oxidative stress | en |
| dc.subject | high fat diet | en |
| dc.subject | streptozotocin | en |
| dc.subject | β-cell apoptosis | en |
| dc.subject | interleukin 33 | en |
| dc.subject | diabetes therapy | en |
| dc.title | Uloga galektina-3 u patofiziologiji ß ćelija pankreasa | sr |
| dc.title.alternative | The role of galectin-3 in pancreatic ß cells pathophysiology | en |
| dc.type | PhD thesis | |
| dc.rights.license | BY-ND | |
| dcterms.abstract | Јовичић, Немања; Лалић, Небојша М.; Живанчевић Симоновић, Снежана; Лукић, Миодраг Л.; Ђукић, Aлександар; Петровић, Ивица; Улога галектина-3 у патофизиологији ß ћелија панкреаса; Улога галектина-3 у патофизиологији ß ћелија панкреаса; | |
| dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/70971/izvestaj_Ivica_Petrovic_Medicina.pdf | |
| dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/70970/Disertacija.pdf | |
| dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_18238 |
