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Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines
Thesis (MSc)--Stellenbosch University, 2021.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2021
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| _version_ | 1867613953791623168 |
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| access_status_str | Open Access |
| author | Green, Nicole Joy |
| author2 | Verhoog, Nicolette J. D. |
| author_browse | Green, Nicole Joy Verhoog, Nicolette J. D. |
| author_facet | Verhoog, Nicolette J. D. Green, Nicole Joy |
| author_sort | Green, Nicole Joy |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2021. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/110214 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:44:20.637Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/110214 Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines Green, Nicole Joy Verhoog, Nicolette J. D. Louw, Ann Stellenbosch University. Faculty of Science. Dept. of Biochemistry. Liver -- Diseases Insulin resistance Insulin signalling Pro-inflammatory cytokines Glucocorticoids -- Receptors Insulin -- Receptors -- Effect of drugs on UCTD Thesis (MSc)--Stellenbosch University, 2021. ENGLISH ABSTRACT: In the liver, insulin is responsible for maintaining glucose homeostasis by activating glycogen synthesis and inhibiting de novo glucose synthesis. Interruption or improper functioning of the insulin signalling pathway is one mechanism by which insulin resistance (inadequate response of target tissues to normal insulin levels) occurs. Prolonged exposure to glucocorticoids (GCs) has been linked to increased hepatic glucose production, and subsequently insulin resistance. Furthermore, chronic inflammation (represented by pro-inflammatory cytokines) has been implicated in the interruption of insulin signalling, also leading to insulin resistance. However, these two biological mediators, which are seldom present in isolation, serve opposing functions in the body with GCs having anti-inflammatory action. The fact that chronic stress and chronic inflammation result in the same consequence in the form of insulin resistance led us to question whether these biological mediators are able to co-regulate insulin signalling at key insulin regulated nodes namely, AKT- and GSK-3 protein expression and phosphorylation as well as the G6Pase mRNA expression in both murine (BWTG3) and human (HepG2) hepatoma cell lines. Overall, co-regulation by the GCs and cytokines was observed at all nodes except GSK-3. The results, however, were GC, cytokine, and cell line specific. As expected, antagonistic behaviour was displayed between the GCs and cytokines, but interestingly, co-operative effects were also observed. Whether these biological mediators lead to an insulin resistant state when present simultaneously in vivo, remains to be determined. AFRIKAANSE OPSOMMING: In die lewer is insulien verantwoordelik vir die handhawing van glukose-homeostase deur glikogeen-sintese te aktiveer en de novo-glukose-sintese te inhibeer. Onderbreking of onbehoorlike werking van die insulienseinweg is een meganisme waardeur insulienweerstandigheid (onvoldoende reaksie van die teikenweefsel op normale insulienvlakke) plaasvind. Langdurige blootstelling aan glukokortikoïede (GC’s) is gekoppel aan verhoogde lewerglukoseproduksie, en gevolglik insulienweerstandigheid. Voorts word daar gedink dat chroniese inflammasie (verteenwoordig deur pro-inflammatoriese sitokiene) die onderbreking van die insuliensein tot gevolg het, wat ook tot insulienweerstandigheid lei. Hierdie twee biologiese seintransduksiemolekules, wat selde in isolasie teenwoordig is, dien egter teenoorgestelde funksies in die liggaam, met GC’s wat ’n anti-inflammatoriese werking het. Die feit dat chroniese spanning en chroniese inflammasie dieselfde gevolg het, in die vorm van insulienweerstandigheid, het ons laat twyfel of hierdie biologiese molekules die vermoë het om mede-reguleerders te kan wees van insulienseinsending by sleutel-insuliengereguleerde nodusse, naamlik AKT- en GSK-3 proteïen-uitdrukking en fosforilering sowel as die G6Pase mRNA-uitdrukking in beide muriene (BWTG3) en menslike (HepG2) hepatoom-sellyne. In die algemeen is mede-regulering deur die GC’s en sitokiene by alle nodusse waargeneem, behalwe GSK-3α. Die resultate was egter GC-, sitokien- en sellyn-spesifiek. Soos verwag is antagonistiese gedrag tussen die GC’s en sitokiene vertoon, maar interessant genoeg is samewerkingseffekte ook waargeneem. Of hierdie biologiese molekules tot ’n insulienweerstandige toestand lei as dit gelyktydig in vivo voorkom, moet nog bepaal word. Masters 2021-04-22T09:31:51Z 2021-04-22T09:31:51Z 2021-04 Thesis http://hdl.handle.net/10019.1/110214 en_ZA Stellenbosch University vii, 109 pages : illustrations (some color) application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Liver -- Diseases Insulin resistance Insulin signalling Pro-inflammatory cytokines Glucocorticoids -- Receptors Insulin -- Receptors -- Effect of drugs on UCTD Green, Nicole Joy Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines |
| title | Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines |
| title_full | Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines |
| title_fullStr | Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines |
| title_full_unstemmed | Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines |
| title_short | Co-regulation of insulin signalling by glucocorticoids and pro-inflammatory cytokines |
| title_sort | co regulation of insulin signalling by glucocorticoids and pro inflammatory cytokines |
| topic | Liver -- Diseases Insulin resistance Insulin signalling Pro-inflammatory cytokines Glucocorticoids -- Receptors Insulin -- Receptors -- Effect of drugs on UCTD |
| url | http://hdl.handle.net/10019.1/110214 |
| work_keys_str_mv | AT greennicolejoy coregulationofinsulinsignallingbyglucocorticoidsandproinflammatorycytokines |