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Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus?
Thesis (MSc)--Stellenbosch University, 2012.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2012
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| _version_ | 1867613755505901568 |
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| access_status_str | Open Access |
| author | Springhorn, Clare |
| author2 | Essop, M. Faadiel |
| author_browse | Essop, M. Faadiel Springhorn, Clare |
| author_facet | Essop, M. Faadiel Springhorn, Clare |
| author_sort | Springhorn, Clare |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2012. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/71808 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:41:10.692Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2012 |
| publishDateRange | 2012 |
| publishDateSort | 2012 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/71808 Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus? Springhorn, Clare Essop, M. Faadiel Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Diabetes Mellitus, Type 2 Diabetes -- Diagnosis Leukocyte O-GlcNAcylation Theses -- Physiology Dissertations -- Physiology Thesis (MSc)--Stellenbosch University, 2012. ENGLISH ABSTRACT: Context: There are serious deficiencies in the current tests and criteria available for the diagnosis of diabetes. A novel screening method for the earlier and more efficient detection of type 2 diabetes would be a significant clinical advance. Objective: The hexosamine biosynthetic pathway (HBP) usually acts as a fuel sensor and its activation leads to O-GlcNAcylation of target proteins in a glucose-responsive manner. O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) are responsible for O-GlcNAc addition and removal, respectively. As higher HBP flux is linked to insulin resistance/type 2 diabetes, we hypothesized that increased O-GlcNAcylation of leukocyte proteins can detect the onset of pre- and overt diabetes. Materials and methods: 74 participants from Bellville and Stellenbosch (Western Cape, South Africa) were recruited and characterized as normal, pre-diabetic or diabetic. Leukocytes (granulocytes and lymphocytes) isolated from study subjects were evaluated for O-GlcNAcylation, OGA and OGT expression by flow cytometry, immunofluorescence microscopy and Western blotting. Results: Leukocyte O-GlcNAcylation increased in both pre-diabetic and diabetic individuals, with leukocyte sub-population data showing the greatest sensitivity. OGA expression and O-GlcNAc/OGA ratios elevated in parallel with increasing glucose concentrations. OGT expression did not significantly change for any of the study subjects investigated. Conclusions: The initial and significant increases in leukocyte O-GlcNAcylation demonstrate great potential for the earlier detection of pre-diabetic and diabetic individuals. OGA expression and O-GlcNAc/OGA ratios may also have diagnostic value. Together our data show strong promise for eventual diagnostic utility and the more efficient detection of type 2 diabetes. AFRIKAANSE OPSOMMING: Die konteks: Daar is ernstige tekortkominge in die huidige toetsing en kriteria vir die diagnose van diabetes. ʼn Nuwe metode vir die vroeë en meer effektiewe opsporing van tipe 2 diabetes sal beduidende kliniese voordeel inhou. Doelstelling: Onder normale omstandighede tree die heksosamienbiosintetiese pad (HBP) as energie sensor op, en die aktivering daarvan gee aanleiding tot O-GlcNAsetilering van proteïene in ʼn glukose-afhanglike wyse. O-GlcNAs transferase (OGT) en O-GlcNAse (OGA) is onderskeidelik verantwoordelik vir O-GlcNAs toevoeging en verwydering. Aangesien hoër HBP fluks verband hou met insulienweerstandigheid /tipe 2 diabetes, stel ons ʼn hipotese voor dat opsporing van verhoogde O-GlcNAsilasie van leukosietproteïene, die aanvang van pre-diabetes en diabetes kan voorspel. Materiale en metodes: 74 vrywillige deelnemers van Bellville en Stellenbosch (Wes Kaap Provinsie, Suid Afrika) is gewerf en gekarakteriseer as normaal, pre-diabeties of diabeties. Leukosiete (granulosiete en limfosiete), uit bloed van deelnemers geïsoleer, is vir O-GlcNAsilasie, OGA en OGT uitdrukking deur vloeisitometrie, immunofluoressensie-mikroskopie en Western blotting, ondersoek. Resultate: Leukosiet O-GlcNAsetilering is verhoog in beide pre-diabetiese en diabetiese individue, met leukosiet sub-populasie wat die mees sensitiewe data gelewer het. OGA uitdrukking en O-GlcNAs/OGA verhoudings in parallel verhoog tot ʼn toename in glukose konsentrasies. OGT uitdrukking het nie betekenisvol verander in enige van die individue wat ondersoek is nie. Gevolgtrekkings: Die vroeë en betekenisvolle toename in leukosiet O-GlcNAsetilering toon groot potensiaal vir die vroeë opsporing van pre-diabetiese en diabetiese individue. OGA uitdrukking en O-GlcNAs/OGA verhoudings het ook moontlik diagnostiese waarde. Ons data toon belowende resultate vir die gevolglike diagnostiese waarde en ʼn meer effektiewe opsporing van tipe 2 diabetes. 2012-11-19T12:24:32Z 2012-12-12T08:11:40Z 2012-11-19T12:24:32Z 2012-12-12T08:11:40Z 2012-12 Thesis http://hdl.handle.net/10019.1/71808 en_ZA Stellenbosch University xx, 180 p. : col. ill. application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Diabetes Mellitus, Type 2 Diabetes -- Diagnosis Leukocyte O-GlcNAcylation Theses -- Physiology Dissertations -- Physiology Springhorn, Clare Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus? |
| title | Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus? |
| title_full | Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus? |
| title_fullStr | Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus? |
| title_full_unstemmed | Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus? |
| title_short | Leukocyte O-GlcNAcylation : a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus? |
| title_sort | leukocyte o glcnacylation a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus |
| topic | Diabetes Mellitus, Type 2 Diabetes -- Diagnosis Leukocyte O-GlcNAcylation Theses -- Physiology Dissertations -- Physiology |
| url | http://hdl.handle.net/10019.1/71808 |
| work_keys_str_mv | AT springhornclare leukocyteoglcnacylationanoveldiagnostictoolfortheearlierdetectionoftype2diabetesmellitus |