Browsing by Author "De Villiers, William"

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    Mathematical modelling of glycolysis in differentiated mouse adipocytes 3T3-L1
    (Stellenbosch : Stellenbosch University, 2021-03) De Villiers, William; Snoep, Jacob Leendert; Van Niekerk, David Douglas; Stellenbosch University. Faculty of Science. Dept. of Biochemistry.
    ENGLISH ABSTRACT: Diabetes mellitus is a metabolic disease characterised by high blood sugar levels, primarily caused by insulin resistance and the resulting inability of the body to process glucose. Any tissue or cell that utilizes glucose is a target of diabetes research. Obesity is closely related to the development of diabetes due to the swelling of adipocytes caused by triacylglycerol formation. As glucose and its breakdown by glycolysis are directly responsible for supplying triacylglycerol formation, the focus of this work was on glycolysis in 3T3-L1 adipocytes. A bottom-up modelling approach was used in which all enzymes within glycolysis and the initial lipogenic enzyme G3PDH were characterised in order to create a kinetic model for glycolysis in 3T3-L1 adipocytes. Nondiabetic adipocyte cell extracts were utilized due to the need for a reference state model. Validation was performed using an HPLC analysis of glycolytic intermediates and co-factors. The validation was partially successful with glucose consumption and several glycolytic intermediate dynamics well described. Lactate production was underestimated in the model due to the high G3PDH activity within cell extracts which caused a signi cant fraction of the glucose to be converted via the glycerol branch, which was not seen to the same degree in the HPLC analysis. Being the rst model of its kind to be constructed for adipocytes, this work has laid the groundwork for further modelling of adipocyte glucose metabolism to better understand the diabetic condition in adipose tissue.