Akutni učinak intracerebroventrikularne primjene inhibitora receptora za inkretin na pokazatelje oksidativnog stresa i inzulinske signalizacije u jetri štakorskog modela sporadične Alzheimerove bolesti

master's thesis

• Title (english): Acute effect of intracerebroventricular application of incretin receptor inhibitor on indicators of oxidative stress and insulin signalization in the liver of the rat model of sporadic Alzheimer's disease
• Author: Mihovil Joja
• Mentor: Melita Šalković-Petrišić (mentor)
• Committee member: Jelena Osmanović Barilar (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Melita Šalković-Petrišić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pharmacology); Zagreb
• Defense date and country: 2022-09-02, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract

Incidencija demencije uzrokovane sporadičnim oblikom Alzheimerove bolesti (sAB) ima zabrinjavajući trend porasta u proteklih 20 godina te predstavlja značajan zdravstveni i ekonomski teret društava. Novije spoznaje o podlozi neurodegenerativnih promjena u sAB ukazuju na moguću ulogu perifernih organa, posebno jetre, kao jednog od čimbenika u patofiziologiji sAB. Jedan od najkorištenijih modela sAB je štakorski model dobiven inntracerebroventikulanom primjenom streptozotocina (STZ-icv). Primjena inkretinskih analoga u STZ-icv životinja dovela je do poboljšanja kognitivnih funkcija i otvorila put njihovom daljnjem testiranju na ljudima. U ovom radu istraživana je akutna inhibicija receptora za inzulinotropni polipeptid ovisan o glukozi (GIP) na parametre oksidativnog stresa i metaboličke signalizacije u jetri kod zdravih i STZ-icv štakora. Rezultati pokazuju da središnja inhibicija GIP sustava u zdravih životinja ne dovodi do oksidativnog stresa ali poremećuje inzulinsku signalizaciju u jetri (smanjuje izražaj IR, povećava fosforilaciju IRS1 i snižava razinu IDE), uz povećanje razine GIP-a i inzulina u plazmi. U štakora s eksperimentalnom sAB, centralna inhibicija GIP-a također nije imala učinka na oksidativni stres, ali smo primijetili promjene manjeg intenziteta u vidu inzulinske signalizacije.

Abstract (english)

A significant medical and economic burden comes from an increasing incidence of sporadic Alzheimer's disease (sAD) that is observed over the last 20 years. Recent studies stress the importance of peripheral organs, namely the liver, in the pathophysiology of sAD. Intracerebroventricular (ICV) application of streptozotocin in rats induces Alzheimer-like changes in animals, and it is the most common sAD model in use. Incretin analogs treatment improved cognitive functions in ICV/STZ sAD model. In this study, we investigated the influence of GIP receptor inhibition treatment on oxidative stress and metabolic signaling in the liver of the ICV STZ model. Central inhibition of GIP in healthy animals did not increase oxidative stress but did disrupt insulin signaling in the liver by decreasing expression of insulin receptor and IDE, and increasing the phosphorylation of IRS1. In rats with experimental sAD, central inhibition of GIP also did not affect oxidative stress but we observed the same changes in insulin signaling to a lesser degree.

• Keywords: Alzheimerova bolest; jetra; streptozotocin; inkretini
• Keywords (english): Alzheimer 's disease; liver; streptozotocin; incretins
• Language: croatian
• URN:NBN: urn:nbn:hr:105:404629
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-01-13 10:02:28