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doctoral thesis
Mehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre
2008. urn:nbn:hr:171:918463
Puljak, Livia
University of Split
School of Medicine

Cite this document

Puljak, L. (2008). Mehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre (Doctoral thesis). Split: University of Split, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:171:918463

Puljak, Livia. "Mehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre." Doctoral thesis, University of Split, School of Medicine, 2008. https://urn.nsk.hr/urn:nbn:hr:171:918463

Puljak, Livia. "Mehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre." Doctoral thesis, University of Split, School of Medicine, 2008. https://urn.nsk.hr/urn:nbn:hr:171:918463

Puljak, L. (2008). 'Mehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre', Doctoral thesis, University of Split, School of Medicine, accessed 17 November 2024, https://urn.nsk.hr/urn:nbn:hr:171:918463

Puljak L. Mehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre [Doctoral thesis]. Split: University of Split, School of Medicine; 2008 [cited 2024 November 17] Available at: https://urn.nsk.hr/urn:nbn:hr:171:918463

L. Puljak, "Mehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre", Doctoral thesis, University of Split, School of Medicine, Split, 2008. Available at: https://urn.nsk.hr/urn:nbn:hr:171:918463

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Metadata
TitleMehanizmi inzulinske rezistencije u amiodaronskom modelu masne jetre
Title (english)Mechanisms of insulin resistance in the amiodarone model of fatty liver
AuthorLivia Puljak
MentorDamir Sapunar (mentor)
Committee memberSiniša Volarević (predsjednik povjerenstva)
Committee memberŽeljko Dujić (član povjerenstva)
Committee memberJanoš Terzić (član povjerenstva)
GranterUniversity of Split
School of Medicine
Split
Defense date and country2008, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Cytology, Histology and Embryology
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
U ovoj disertaciji opisani su stanični mehanizmi odgovornih za inhibiciju staničnih odgovora na inzulin u stanicama masne jetre. Početni odgovor jetrenih stanica na inzulin posredovan je egzocitozom vezikula koje sadrže kloridne kanale te otvaranjem kloridnih kanala na staničnoj membrani. Unutarstanično nakupljanje masnih kiselina vodi do složenog poremećaja metabolizma i usko je povezano s inzulinskom rezistencijom. Nije poznato na koji način je aktivnost kloridnih kanala promijenjena kod inzulinske rezistencije te kojim mehanizmom. Mi smo istražili učinak nakupljanja masnih kiselina na otvaranje kloridnih kanala u staničnoj liniji jetre (HTC stanice). Tretiranje amiodaronom preko noći povećalo je masni sadržaj stanice dvostruko te ubrzalo gluokoneogenezu peterostruko. Sposobnost inzulina da potisne glukoneogenezu je bila značajno smanjena što ukazuje na to da liječenje amiodaronom uzrokuje inzulinsku rezistenciju. Western blot analiza pokazala je kako HTC stanice imaju isti broj inzulinskih receptora kao i kontrolne. Meñutim, inzulin nije uspio u HTC stanicama aktivirati egzocitozu i otvaranje kloridnih kanala. Ovi su inhibitorni učinci zamijećeni i u kontrolnim stanicama nakon tretiranja s arahidonskom kiselinom. Daljnje studije su pokazale kako masne kiseline stimuliraju aktivnost PKC, a inhibicija PKC djelomično oporavlja egzocitozu i otvaranje kloridnih kanala u inzulin-rezistentnim stanicama. Aktivacija PKC pomoću PMA u kontrolnim stanicama potentno je inhibirala odgovor na inzulin. Ovi rezultati pokazuju kako je stimulacija PKC aktivnosti u inzulinskoj rezistenciji odgovorna za inhibiciju staničnih odgovora na inzulin u jetrenoj stanici.
Abstract (english)
In this dissertation cellular mechanisms resposible for inhibition of cellular responses to insulin in fatty liver cells are described. The initial response of liver cells to insulin is mediated through exocytosis of Cl-channel-containing vesicles and a subsequent opening of plasma membrane Cl-channels. Intracellular accumulation of fatty acids leads to profound defects in metabolism, and is closely associated with insulin resistance. It is not known whether the activity of Cl-channels is altered in insulin resistance and by which mechanisms. We studied the effects of fatty acid accumulation on the Cl-channel opening in a model liver cell line. Overnight treatment with amiodarone increased fat content by ~2 fold, and the rates of gluconeogenesis by ~5 fold. The ability of insulin to suppress gluconeogenesis was markedly reduced indicating that amiodarone treatment induces insulin resistance. Western blot analysis showed that these cells express the same number of insulin receptors as control cells. However, insulin failed to activate exocytosis and Cl-channel opening. These inhibitory effects were mimicked in control cells by exposures to arachidonic acid. Further studies demonstrated that fatty acids stimulate the PKC activity, and inhibition of PKC partially restored exocytosis and Cl-channel opening in insulin-resistant cells. Accordingly, activation of PKC with PMA in control cells potently inhibited the insulin responses. These results suggest that stimulation of PKC activity in insulin resistance contributes to the inhibition of cellular responses to insulin in liver cells.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:171:918463
Study programmeTitle: Obtaining a doctorate of science outside of doctoral studies
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti (doktor/doktorica znanosti)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-04-24 08:50:31