Ultrastrukturne promene u limfocitima periferne krvi bolesnika sa Diabetes mellitus-om tip 2
Ultrastructural alterations in peripheral blood lymphocytes in type 2 diabetes patients
Author
Martinović, Tamara I.Mentor
Kravić-Stevović, Tamara
Committee members
Lalić, Katarina
Bumbaširević, Vladimir
Trajković, Vladimir

Krstić, Miljan

Metadata
Show full item recordAbstract
Tip 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...
Type 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...
Faculty:
Универзитет у Београду, Медицински факултетDate:
24-09-2018Projects:
- Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-41025)
- Immunopathogenic and regulatory mechanisms in autoimmune diseases and chronic inflamation (RS-175038)