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Investigating differential non-oxidative glucose-utilizing pathway gene expression as a novel diagnostic tool for type 2 diabetes

Coomer, Megan (2013-12)

Thesis (MSc)--Stellenbosch University, 2013.

ENGLISH ABSTRACT: Context: Despite the availability and accessibility of current diagnostic tools, diabetes remains largely under-diagnosed. Biological limitations, discordant assays and conflicting diagnostic thresholds together impede the accurate and successful diagnosis of diabetes, providing impetus into research for a novel diagnostic tool. Aim: Since flux through the five minor glycolytic pathways is increased during hyperglycemia, we hypothesized that the genes encoding the regulatory enzymes of such pathways may be differentially expressed between control, pre-diabetic and diabetic individuals setting the scene for an exploratory diagnostic avenue employing genetic biomarkers. Experimental procedures: Participants (n=60; n=20 Mixed Ancestry, n=40 Caucasian) were recruited from Stellenbosch and Paarl (Western Cape, South Africa) and classified as control, pre-diabetic or diabetic. RNA was purified from leukocytes isolated from blood samples and OGT, OGA, GFPT1, GFPT2, TKT, TKTL1 and AKR1B1 expression determined by quantitative real-time PCR. Results: Expression of OGA, OGT, GFPT2 and TKTL1 decreased in pre-diabetic and diabetic individuals; while GFPT1, TKT and AKR1B1 expression levels remained largely unaffected between the study groups. GFPT2 exhibited ethnic-dependent regulation. Conclusion: Differential expression of genes regulating non-oxidative glucose-utilizing pathways may offer diagnostic utility in the future and warrant further investigation.

AFRIKAANSE OPSOMMING: Konteks: Teen spyte van die beskikbaarheid en toeganklikheid van huidige diagnostiese instrumente, word diabetes nogsteeds min gediagnoseer. Altesaam belemmer biologiese beperkings, teenstrydige toetse en botsende diagnostiese grense die akkurate en suksesvolle diagnose van diabetes, wat bydra tot die druifkrag in navorsing vir ‘n nuwe diagnostiese instrument. Doelstelling: Aangesien die vloei deur die 5 mineur glikolitiese pad weë toeneem gedurende hiperglukemie, veronderstel ons dat die gene wat regulatoriese ensieme kodeer in hierdie pad weë mag dalk differensieel uitgedruk word tussen kontrol, voor- en, diabetiese individue wat die toneel skep vir ‘n ondersoekende diagnotiese laan wat gebruik maak van genetiese merkers. Materiale en metodes: Deelnemers (n=60; n=20 Gemengde afkoms; n=40 Blankes) was uit Stellenbos en die Paarl gewerf (Wes-Kaap, Suid-Afrika) en geklassifiseer as ‘n kontrol, voorof diabeties. RNS was uit witbloodselle gesuiwer wat eers uit bloed monsters geisoleer was en OGT, OGA, GFPT1, GFPT2, TKT, TKTL1 en AKR1B1 uitdrukking was bepaal deur kwantitatiewe RT-PKR. Resultate: Uitdrukking van OGA, OGT, GFPT2 en TKTL1 het afgeneem in voor- en diabetiese individue; terwyl GFPT1, TKT en AKR1B1 utidrukkings vlakke meestal onaangeraak was tussen die studie groepe. GFPT2 het etiese-afhanglike regulasie vertoon. Gevolgtrekkings: Differensiele uitdrukking van gene wat glukose gebruik in nieoksidatiewe pad weë reguleer bied diagnotiese gebruikbaarheid in die toekoms en bevel verdere ondersoek.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/95491
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