MikroRNA – novi biomarker za ranu detekciju i praćenje pacijenata sa tipom 2 šećerne bolesti

master's thesis

• Title (english): MicroRNA - new biomarker for early detection and monitoring of patients with type 2 diabetes
• Author: Dominik Veselko Barać
• Mentor: Roberta Petlevski (mentor)
• Committee member: Roberta Petlevski (predsjednik povjerenstva)
• Committee member: Anita Somborac Bačura (član povjerenstva)
• Committee member: Dubravka Vitali Čepo (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2022-12-21, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Šećerna bolest tipa 2 jedno je od najčešćih oboljenja i najvećih izazova suvremene medicine. Glavne karakteristike T2DM su nesposobnost tkiva osjetljivih na inzulin da na odgovarajući način reagiraju na inzulin (inzulinska rezistencija), smanjena funkcija β stanica Langerhansovih otočića te smanjena sekrecija inzulina. Definitivan i konačan uzrok smanjene funkcije β-stanica u T2DM je zasad nepoznat a smatra se da ulogu imaju genetski i okolišni čimbenici. T2DM je jako komplicirana bolest sa multiorganskim efektima a glavni simptomi koji se javljaju su povećani osjećaji gladi i žeđi, učestalo mokrenje, gubitak na tjelesnoj masi, pretjerani umor te je glavni uzročnik ovih simptoma hiperglikemija. Javlja se potreba za biomarkerima koji će nam pomoći da ranije otkrijemo bolest i kvalitetnije pratimo učinak terapije. MikroRNA (miRNA) su male nekodirajuće RNA molekule koje su duge oko 21-25 nukleotida te funkcioniraju kao translacijski represori. MiRNA su danas univerzalno prepoznate kao glavni regulatori genske ekspresije i kao ključni kontrolori nekoliko bioloških i patoloških procesa. MiRNA nemaju samo funkciju regulacije gena unutar stanica u kojoj nastaju, već se mogu naći i u tjelesnim tekućinama poput krvi, zajedno sa proteinima, mikrovezikulama ili lipoproteinskim kompleksima. Neke značajke miRNA koje ih čine dobrim biomarkerima su da se osim u krvi, nalaze se i u drugim tjelesnim tekućinama koje možemo analizirati kao što su slina, urin, majčino mlijeko i amnionska tekućina, mogu se određivati visokoosjetljivim i specifičnim kvantitativnim PCR metodama, zdravi donori nemaju značajnije varijacije miRNA profila tijekom dana te se mogu mjeriti i u serumu i u plazmi. Ono što je jako važno je da se profil ekspresije miRNA u β-stanicama i ciljanim tkivima inzulina mijenjaju i u T1DM i T2DM što najvjerojatnije pridonosi oštećenju funkcija ovih tkiva. Iako teoretski dobar biomarker za šećernu bolest tipa 2, istraživanja su pokazala da je samo mali broj pouzdanih miRNA profila ekspresije konzistentan. Zbog tehnoloških problema u rukovanju uzorcima, mjerenju miRNA i interpretaciji podataka, moguće je propustiti značaj miRNA. MiRNA koje bi se koristile trebale bi zamijeniti ili dopuniti postojeće standardne biomarkere. Stoga je potrebno sustavno uspoređivati njihovu sposobnost predviđanja pojave šećerne bolesti ili njenih posljedica s onima već postojećih biomarkera.

Abstract (english)

Type 2 diabetes is one of the most common diseases and the greatest challenges of modern medicine. The main characteristics of T2DM are the inability of insulin-sensitive tissues to respond appropriately to insulin (insulin resistance), reduced β-cell function of the islets of Langerhans, and reduced insulin secretion. The definitive and definitive cause of reduced β-cell function in T2DM is currently unknown, and it is believed that genetic and environmental factors play a role. T2DM is a very complicated disease with multiorgan effects, and the main symptoms that occur are increased feelings of hunger and thirst, frequent urination, weight loss, excessive fatigue, and the main cause of these symptoms is hyperglycemia. There is a need for biomarkers that will help us detect the disease earlier and better monitor the effect of therapy. MicroRNAs (miRNAs) are small non-coding RNA molecules that are about 21-25 nucleotides long and function as translational repressors. MiRNAs are now universally recognized as the main regulators of gene expression and as key controllers of several biological and pathological processes. MiRNAs not only have the function of gene regulation inside the cells in which they are produced, but can also be found in body fluids such as blood, together with proteins, microvesicles or lipoprotein complexes. Some features of miRNAs that make them good biomarkers are that apart from blood, they are also found in other body fluids that we can analyze such as saliva, urine, breast milk and amniotic fluid, they can be determined by highly sensitive and specific quantitative PCR methods, healthy donors do not have more significant variations of the miRNA profile during the day and can be measured in both serum and plasma. What is very important is that the expression profile of miRNAs in β-cells and target tissues of insulin are changed in both T1DM and T2DM, which most likely contributes to the impairment of the functions of these tissues. Although theoretically a good biomarker for type 2 diabetes, research has shown that only a small number of reliable miRNA expression profiles are consistent. Due to technological problems in sample handling, miRNA measurement and data interpretation, it is possible to miss the significance of miRNAs. The miRNAs that would be used should replace or complement existing standard biomarkers. Therefore, it is necessary to systematically compare their ability to predict the onset of diabetes or its consequences with those of already existing biomarkers.

• Keywords: šećerna bolest tipa 2; mikroRNA; biomarker; dijagnostika; β-stanice; genska ekspresija
• Keywords (english): type 2 diabetes; microRNA; biomarker; diagnostics; β-cells; gene expression
• Language: croatian
• URN:NBN: urn:nbn:hr:163:801347
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije (magistar/magistra medicinske biokemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-01-09 15:10:40