Inkretini i šećerna bolest tip 2 - od patofiziologije do rerapijske primjene

master's thesis

• Title (english): Incretins and diabetes mellitus type 2 - from pathophysiology to therapeutic treatment
• Author: Karla Ranđelović
• Mentor: Lea Smirčić-Duvnjak (mentor)
• Committee member: Ivana Pavlić-Renar (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Lea Smirčić-Duvnjak (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2014-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Moderni terapijski pristup liječenju šećerne bolesti tipa 2 usmjeren je na povećanje razine
inkretinskih hormona u cirkulaciji. Inkretini su endogeni regulatorni peptidi koje izlučuju
stanice crijeva i koji potiču otpuštanje inzulina, inhibiraju izlučivanje glukagona i time
glukoneogenezu u jetri, a za razliku od drugih lijekova dovode do usporenog pražnjenja
želuca, smanjenja apetita, povećanja osjećaja sitosti i smanjenog unosa hrane što dovodi i do
smanjenja tjelesne mase. U šećernoj bolesti tipa 2 njihovo je izlučivanje ili djelovanje
poremećeno. U ljudskom organizmu dva su osnovna inkretina: glukagonu sličan peptid-1
(GLP-1) koji se izlučuje iz L-stanica distalnog crijeva (ileuma i kolona) i inzulinotropni
peptid ovisan o inzulinu (GIP) koji se izlučuje iz K-stanica tankog crijeva (duodenum i
proksimalni jejunum). Brza razgradnja enzimom DPP-4 ograničava učinak GLP-1 i GIP-a na
homeostazu glukoze. Iako i GIP i GLP-1 imaju izražen inzulinotropni učinak, samo je GLP-1
smatran potencijalnim kandidatom za terapijsku primjenu u liječenju šećerne bolesti tipa 2.
Dvije su terapijske mogućnosti bazirane na inkretinima: inkretinski analozi otporni na DPP-4,
te inkretinski pojačivači, tvari koje sprječavaju razgradnju endogenih inkretina inhibicijom
enzima dipeptidil-peptidaze-4 (DPP-4) koji ih razgrađuje. Obje skupine lijekova predstavljaju
učinkovitu alternativu trenutno dostupnim hipoglikemičkim lijekovima. S obzirom da je
njihov učinak ovisan o glukozi, rizik od hipoglikemije je vrlo nizak. GLP-1 ima i
mnogobrojne ekstrapankreatičke metaboličke učinke. Poznato je da se receptori za GLP-1
nalaze i na drugim organima i danas se istražuju brojni učinci GLP-1 na te organske sustave.

Abstract (english)

The modern therapeutic approach to treatment of diabetes type 2 is focused at increasing
levels of incretin hormones in the circulation. The incretins are endogenous regulatory
peptides secreted by cells of the intestine, and their purpose is to stimulate insulin release,
inhibite glucagon secretion and gluconeogenesis in the liver, and in opposite to other drugs it
leads to slow gastric emptying, decrease appetite, increase satiety and reduced food intake
leading to reduction in body weight. In diabetes mellitus type 2 their secretion or action is
disturbed. Human body has two main incretins: glucagon-like peptide-1 (GLP-1) which is
secreted from the L-cells of the distal gut (ileum and colon) and glucose-dependent
insulinotropic poypeptide (GIP) which is secreted from the K-cells of the small intestine
(duodenum and proximal jejunum). Quick degradation by the enzyme DPP-4 limits the effect
of GLP-1 and GIP on glucose homeostasis. Although GIP and GLP-1 have expressed
insulinotropic effect, only GLP-1 is considered as a potential candidate for therapeutic
treatment of diabetes mellitus type 2. There are two therapeutic options based on incretins:
incretin analogues resistant to DPP-4 and incretin enhancers, substances which prevent
degradation of endogenous incretins by inhibiting dipeptidyl peptidase - 4 (DPP-4) which
breaks them down. Both groups of drugs represent an effective alternative to the currently
available hypoglycaemic drugs. Due to their glucose-dependent effect, the risk of
hypoglycaemia is very low. GLP-1 has numerous extrapancreatic metabolic effects. It is
known that receptors for the GLP-1 are found in other organs and today numerous effects of
GLP-1 in organism are being investigated.

• Keywords: GLP-1; GIP; inkretini; šecerna bolest tip 2; pretilost
• Keywords (english): GLP-1; GIP; incretins; diabetes mellitus type 2; obesity
• Language: croatian
• URN:NBN: urn:nbn:hr:105:376521
• 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: 2015-10-28 12:10:50