Pankreatični i sustavni učinci terapije analoga glukagonu sličnog peptida-1

master's thesis

• Title (english): Pancreatic and systemic effects of glucagon-like peptide-1 agonist therapy
• Author: Ana Peremin
• Mentor: Tomislav Bulum (mentor)
• Committee member: Spomenka Ljubić (predsjednik povjerenstva)
• Committee member: Martina Lovrić Benčić (član povjerenstva)
• Committee member: Tomislav Bulum (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2024-09-11, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Terapijski pristup šećernoj bolesti tipa 2 sve češće uključuje terapiju temeljenu na inkretinskom sustavu, posebice analoge glukagonu sličnog peptida-1 (GLP-1). Ti pripravci oponašaju sekreciju endogeno proizvedenog inkretinskog hormona GLP-1, dovodeći do pojačane sekrecije inzulina i slabijeg lučenja glukagona, što je bitno za održavanje homeostaze glukoze. Pankreatični učinci analoga GLP-1 receptora očituju se pojačanim lučenjem inzulina iz β-stanica gušterače ovisnog o glukozi i inhibicijom lučenja glukagona iz α-stanica otočića gušterače. Proliferacija β-stanica, inhibicija apoptoze i pojačana sinteza inzulina još su neki od povoljnih učinaka na tkivo gušterače. Osim pankreatičnih učinaka, analozi GLP-1R pokazuju neke sustavne prednosti, osobito u protekciji kardiovaskularnog sustava i smanjenju tjelesne težine. Klinička istraživanja provedena u svrhu dokaza kardiovaskularne sigurnosti, pokazala su da analozi GLP-1 receptora smanjuju rizik od velikog štetnog kardiovaskularnog događaja, koji uključuje smrt kardiovaskularnog uzroka, infarkt miokarda ili moždani udar bez smrtnog ishoda. Kardioprotektivne učinke ostvaruje preko nekoliko mehanizama uključujući regulaciju glikemije, krvnog tlaka, razine lipida i tjelesne težine. Također, analozi GLP-1R pokazali su i renoprotektivna svojstva usporavajući progresiju dijabetičke nefropatije očuvanjem eGFR-a i smanjenjem albuminurije. Terapija analozima GLP-1 receptora utječe i na funkciju gastrointestinalnog sustava. Usporava pražnjenje želuca i motilitet crijeva te pruža osjećaj sitosti što sve zajedno rezultira smanjenim unosom hrane. Ta prednost iskorištava se za bolju kontrolu, odnosno redukciju tjelesne težine. Na kraju, noviji podaci pružaju informaciju o neuroprotektivnom djelovanju i ublažavanju kognitivnih poremećaja, pritom ostavljajući prostora za ostvarivanje terapijskog potencijala i na tom području.

Abstract (english)

The therapeutic approach to type 2 diabetes mellitus increasingly includes therapy based on the incretin system, especially glucagon-like peptide-1 agonists. These agents mimic the secretion of the endogenously produced incretin hormone GLP-1, leading to increased insulin secretion and suppressed glucagon secretion, which is essential for maintaining glucose homeostasis. The pancreatic effects of GLP-1 receptor analogues are manifested by increased glucose-dependent insulin secretion from pancreatic β-cells and inhibition of glucagon secretion from α-cells of the pancreatic islets. β-cell proliferation, inhibition of apoptosis and enhanced insulin synthesis are some of the beneficial effects on pancreatic tissue. Beyond their pancreatic effects, GLP 1R analogues show some systemic benefits, especially in the protection of the cardiovascular system and weight loss. Clinical studies conducted to prove cardiovascular safety have shown that GLP-1 receptor analogues reduce the risk of a major adverse cardiovascular event, which includes cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. It exerts cardioprotective effects through several mechanisms, including the regulation of glycemia, blood pressure, lipid levels and body weight. Also, GLP-1R analogues have shown renal protection by slowing the progression of diabetic nephropathy by preserving eGFR and reducing albuminuria. Therapy with GLP-1 receptor analogues also affects the function of the gastrointestinal system. It slows down gastric emptying and intestinal motility and provides a feeling of satiety, which all together results in reduced food intake. This advantage is used for better body weight management. Finally, recent data provide information on neuroprotective effects and alleviation of cognitive disorders, while leaving room for the realization of therapeutic potential in this area as well.

• Keywords: šećerna bolest tipa 2; analozi glukagonu sličnog peptida-1; pankreatični učinci; sustavni učinci
• Keywords (english): type 2 diabetes mellitus; glucagon-like peptide-1 agonists; pancreatic effects; systemic effects
• Language: croatian
• URN:NBN: urn:nbn:hr:105:276843
• 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: 2024-09-10 07:08:13