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Ultrastructural alterations in peripheral blood lymphocytes in type 2 diabetes patients

dc.contributor.advisorKravić-Stevović, Tamara
dc.contributor.otherLalić, Katarina
dc.contributor.otherBumbaširević, Vladimir
dc.contributor.otherTrajković, Vladimir
dc.contributor.otherKrstić, Miljan
dc.creatorMartinović, Tamara I.
dc.date.accessioned2018-12-10T11:46:10Z
dc.date.available2018-12-10T11:46:10Z
dc.date.available2020-07-03T08:45:44Z
dc.date.issued2018-09-24
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/10277
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6304
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:18962/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=50758671
dc.description.abstractTip 2 dijabetes melitus (T2DM), trenutno jedna od najvećih globalnih epidemija, predstavlja heterogenu grupu poremećaja koja se karakteriše različitim nivoom insulinske rezistencije, poremećenom sekrecijom insulina i hiperglikemijom. Kao početna terapija T2DM koristi se metformin, dok se u kasnijem toku bolesti u terapiji koristi insulin. Nedavni nalazi autoantitela na β ćelije pankreasa i autoreaktivnih T limfocita u T2DM dovode do pretpostavke da u patogenezi T2DM postoji autoimunska komponenta. Savremena istraživanja ukazuju na značaj autofagije u patogenezi T2DM, ali je njena uloga kontroverzna. Rezultati nekih studija ukazuju na povećanu aktivnost autofagije u mononuklearnim ćelijama periferne krvi, dok su u drugim studijama detektovali njenu sniženu aktivnost u ovim ćelijama u dijabetesu. Autofagija je lizozomalni put degradacije intracelularnih komponenti u fiziološkim uslovima i u ćelijskom stresu, i ima ključnu ulogu intracelularnom metabolizmu. Promene u autofagičnom procesu mogu nastati kao odgovor na hiperglikemiju kod bolesnika sa T2DM. Novija elektronsko mikroskopska istraživanja su pokazala da u T2DM dolazi do morfoloških promena u izgledu nukleusa u vidu nepravilnosti oblika i binukelacije nukleusa. Pretpostavka je da su nepravilnosti oblika nukleusa u normalnim humanim limfocitima rezultat aktivacije T limfocita. Cilj: Cilj ovog istraživanja bio je da se metodama ultrastrukturne morfometrije kvantifikuje broj autofagičnih struktura u limfocitima periferne krvi T2DM bolesnika na elektronskom mikroskopu; da se koreliraju dobijeni rezultati sa ekspresijom proteina uključenih u proces autofagije; da se uradi ultrastrukturna analiza aktivacije limfocita i oštećenja subcelularnih struktura kod bolesnika sa T2DM; fraktalna analiza ultrastrukturnog izgleda nukleusa i citoplazme limfocita sa T2DM; i korelacija statusa autofagije sa aktivacijom i oštećenjem subcelularnih struktura u limfocitima bolesnika sa T2DM, kao i sa rezultatima dobijenim fraktalnom analizom nukleusa i citoplazme...sr
dc.description.abstractType 2 diabetes mellitus (T2DM), currently one of the largest global epidemics, is a heterogeneous group of disorders characterized by varying levels of insulin resistance, impaired insulin secretion, and hyperglycemia. Initial therapy for T2DM is metformin, but with the progression of disease, insulin therapy is used. Recent findings of autoantibodies against pancreatic β-cell and autoreactive T cell in T2DM lead to the assumption that there is an autoimmune component in the pathogenesis of T2DM. Recent researches points out the importance of autophagy in the pathogenesis of T2DM, but its role is controversial. Some studies indicate an increased autophagy level in peripheral blood mononuclear cells, while others showed decreased level of autophagy in these cells in diabetes. Autophagy is a lysosomal pathway of degradation of intracellular components in physiological conditions and in cellular stress, and plays a key role in intracellular metabolism. Changes in the autophagy may arise in response to hyperglycemia in patients with T2DM. Recent electron microscopy studies have shown that cells in T2DM have morphological changes in the appearance of the nuclei in the form of shape irregularities and binucleation. It has been proposed that nuclear contour irregularity in normal human lymphocytes, could result from T cell activation. Aim: The aim of this study was to quantify the number of autophagic structures in the peripheral blood lymphocytes of the T2DM patients on an electron microscope, using the methods of ultrastructural morphometry; and to correlate the results obtained with the expression of proteins involved in the autophagy; to perform ultrastructural analysis of lymphocyte activation and subcellular structure damage in T2DM patients; fractal analysis of the ultrastructural appearance of T2DM lymphocyte nuclei and cytoplasm; to correlate autophagy level with activation and damage of subcellular structures in the lymphocytes of T2DM patients, as well as with the results obtained from the fractal analysis of the nuclei and cytoplasm...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41025/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175038/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectdijabetessr
dc.subjectdiabetesen
dc.subjectlymphocyteen
dc.subjectautophagyen
dc.subjectnucleusen
dc.subjectelectron microscopyen
dc.subjectfractal analysisen
dc.subjectglucoseen
dc.subjectlimfocitisr
dc.subjectautofagijasr
dc.subjectnukleussr
dc.subjectelektronska mikroskopijasr
dc.subjectfraktalna analizasr
dc.subjectglukozasr
dc.titleUltrastrukturne promene u limfocitima periferne krvi bolesnika sa Diabetes mellitus-om tip 2sr
dc.title.alternativeUltrastructural alterations in peripheral blood lymphocytes in type 2 diabetes patientsen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/8098/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/8099/IzvestajKomisije18486.pdf


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