{"?xml":{"@version":"1.0"},"edm:RDF":{"@xmlns:dc":"http://purl.org/dc/elements/1.1/","@xmlns:edm":"http://www.europeana.eu/schemas/edm/","@xmlns:wgs84_pos":"http://www.w3.org/2003/01/geo/wgs84_pos","@xmlns:foaf":"http://xmlns.com/foaf/0.1/","@xmlns:rdaGr2":"http://rdvocab.info/ElementsGr2","@xmlns:oai":"http://www.openarchives.org/OAI/2.0/","@xmlns:owl":"http://www.w3.org/2002/07/owl#","@xmlns:rdf":"http://www.w3.org/1999/02/22-rdf-syntax-ns#","@xmlns:ore":"http://www.openarchives.org/ore/terms/","@xmlns:skos":"http://www.w3.org/2004/02/skos/core#","@xmlns:dcterms":"http://purl.org/dc/terms/","edm:WebResource":[{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:DOC-M6Q84YIV/4f03732-f8224fcea236-50fc52dc--11998/PDF","dcterms:extent":"3898 KB"},{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:DOC-M6Q84YIV/4b0515dd-1a98-4d80-b317-9f4f1b6c6420/TEXT","dcterms:extent":"262 KB"},{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:DOC-M6Q84YIV/f64fa0bc-fe6b-4bae-87b7-6c16ab95b470/WEB","dcterms:extent":"0 KB"}],"edm:ProvidedCHO":{"@rdf:about":"URN:NBN:SI:DOC-M6Q84YIV","dcterms:issued":"2022","dc:contributor":"Marhl, Marko","dc:creator":"Zmazek, Jan","dc:format":{"@xml:lang":"sl","#text":"XIV, 122 str., 31 cm"},"dc:identifier":["COBISSID:138073603","URN:URN:NBN:SI:doc-M6Q84YIV"],"dc:language":"sl","dc:publisher":{"@xml:lang":"sl","#text":"J. Zmazek"},"dc:source":{"@xml:lang":"sl","#text":"visokošolska dela"},"dc:subject":[{"@xml:lang":"sl","#text":"cAMP"},{"@xml:lang":"sl","#text":"celice alfa"},{"@xml:lang":"sl","#text":"celice beta"},{"@xml:lang":"sl","#text":"Disertacije"},{"@xml:lang":"sl","#text":"Fiziologija"},{"@xml:lang":"sl","#text":"glukoza"},{"@xml:lang":"sl","#text":"homeostaza"},{"@xml:lang":"sl","#text":"insulinska rezistenca"},{"@xml:lang":"sl","#text":"kalcij"},{"@xml:lang":"sl","#text":"Langerhansovi otočki"},{"@xml:lang":"sl","#text":"Matematični modeli"},{"@xml:lang":"sl","#text":"medcelična komunikacija"},{"@xml:lang":"sl","#text":"metabolizem"},{"@xml:lang":"sl","#text":"presnovni sindrom"},{"@xml:lang":"sl","#text":"računalniška simulacija"},{"@xml:lang":"sl","#text":"signalne poti"},{"@xml:lang":"sl","#text":"sladkorna bolezen tip 2"},{"@xml:lang":"sl","#text":"Trebušna slinavka"}],"dc:title":{"@xml:lang":"sl","#text":"Računska ocena vpliva znotrajceličnih presnovnih in signalnih poti ter medcelične komunikacije na izločanje glukagona in inzulina| doktorska disertacija|"},"dc:description":[{"@xml:lang":"sl","#text":"This doctoral dissertation examines the physiological properties of alpha and beta cells using mathematical modeling, network science, and other contemporary biophysical approaches. The first part of the dissertation presents a newly developed mathematical model of metabolism and hormone secretion in both cell types. The model results indicate that the oxidation of fatty acids is responsible for the high basal production of ATP, while the glucose-dependent increase in ATP is due to the anaerobic (glycolytic) characteristics of the alpha cell or aerobic (mitochondrial) characteristics of the beta cell. Disturbances in glycolytic and mitochondrial metabolism appear to critically influence proper hormone secretion of both cell types. The alpha cell model is further complemented by the cAMP-dependent signaling pathway regulated by metabolic activity or in response to the binding of extracellular signals to membrane receptors. According to the model prediction, acidification of the intracellular space during high metabolic activity is crucial in lowering intracellular cAMP concentration under high plasma glucose concentration conditions. Moreover, the alpha cell model implements the effect of amino acids on alpha cell's activity, matching experimental observation that mixed nutrient challenge potently amplifies glucagon secretion. The second part of the dissertation presents the analysis of the experimentally-obtained calcium signals from beta cells in the islets of Langerhans. The presented data processing methodology includes extraction of metabolically-activated slow and electrically-activated fast components, binarization or discretization of signals, detection of low-quality signals, and construction of functional networks. Slow and fast oscillatory components are interrelated, with the frequency of fast oscillations being highest around the peaks of slow oscillations. This behavior is more pronounced during stimulation with physiological glucose concentration than with supraphysiological concentration. Functional networks are constructed for both components, and their analysis shows more local clustering and segregation of the networks of the fast component and greater globality of the slow component. Multilayer network analysis also indicates a weak coupling between the fast and slow layers, suggesting that different synchronization mechanisms shape the collective activity in the islets"},{"@xml:lang":"sl","#text":"Doktorska disertacija proučuje fiziološke lastnosti celic alfa in beta z uporabo matematičnega modeliranja, omrežnih znanosti in drugih sodobnih biofizikalnih pristopov. V prvem delu disertacije predstavimo matematični model presnove in hormonskega izločanja obeh tipov celic. Rezultati modela kažejo, da je oksidacija maščobnih kislin odgovorna za visoko bazalno nastajanje ATP, medtem ko je od glukoze odvisno zvišanje koncentracije ATP posledica anaerobnih (glikolitskih) značilnosti celice alfa in aerobnih (mitohondrijskih) značilnosti celice beta. Motnje v glikolitski in mitohondrijski presnovi kritično vplivajo na pravilno izločanje hormonov obeh vrst celic. Model celice alfa je nadalje dopolnjen z od cAMP odvisno signalno potjo, ki jo uravnava presnovna aktivnost ali vezava zunajceličnih signalov na membranske receptorje. Glede na modelsko napoved je znižanje znotrajceličnega pH med visoko presnovno aktivnostjo ključnega pomena za znižanje znotrajcelične koncentracije cAMP ob stimulaciji z visoko koncentracijo plazemske glukoze. Modelirana je tudi stimulacija celic alfa z aminokislinami, in sicer tako, da se modelski rezultati ujemajo z eksperimentalnimi opažanji, da obrok mešanih hranil močno poveča izločanje glukagona. Drugi del disertacije predstavlja analizo eksperimentalno pridobljenih kalcijevih signalov iz celic beta v Langerhansovih otočkih. Predstavljena metodologija obdelave podatkov vključuje ekstrahiranje presnovno aktivirane počasne in električno aktivirane hitre komponente, binarizacijo ali diskretizacijo signalov, detekcijo nizkokakovostnih signalov in izgradnjo funkcionalnih mrež. Počasna in hitra oscilatorna komponenta sta med seboj povezani, pri čemer je frekvenca hitrih oscilacij največja okoli vrhov počasnih oscilacij. To vedenje je bolj izrazito pri stimulaciji s fiziološko koncentracijo glukoze kakor pri suprafiziološki koncentraciji. Za obe komponenti so zgrajene funkcionalne mreže, njihova analiza pa kaže na večjo lokalno gručavost in segregacijo mrež hitre komponente ter večjo globalno povezanost počasne komponente. Analiza večplastnih mrež kaže na šibko povezavo med hitro in počasno plastjo, kar nakazuje na to, da različni sinhronizacijski mehanizmi oblikujejo kolektivno aktivnost v otočkih"}],"edm:type":"TEXT","dc:type":[{"@xml:lang":"sl","#text":"visokošolska dela"},{"@xml:lang":"en","#text":"theses and dissertations"},{"@rdf:resource":"http://www.wikidata.org/entity/Q1266946"}]},"ore:Aggregation":{"@rdf:about":"http://www.dlib.si/?URN=URN:NBN:SI:DOC-M6Q84YIV","edm:aggregatedCHO":{"@rdf:resource":"URN:NBN:SI:DOC-M6Q84YIV"},"edm:isShownBy":{"@rdf:resource":"http://www.dlib.si/stream/URN:NBN:SI:DOC-M6Q84YIV/4f03732-f8224fcea236-50fc52dc--11998/PDF"},"edm:rights":{"@rdf:resource":"http://rightsstatements.org/vocab/InC/1.0/"},"edm:provider":"Slovenian National E-content Aggregator","edm:intermediateProvider":{"@xml:lang":"en","#text":"National and University Library of Slovenia"},"edm:dataProvider":{"@xml:lang":"sl","#text":"Univerza v Mariboru, Fakulteta za naravoslovje in matematiko"},"edm:object":{"@rdf:resource":"http://www.dlib.si/streamdb/URN:NBN:SI:DOC-M6Q84YIV/maxi/edm"},"edm:isShownAt":{"@rdf:resource":"http://www.dlib.si/details/URN:NBN:SI:DOC-M6Q84YIV"}}}}