Parker 2020 Thesis
|Parker EP (2020) The effect of isoleucine supplementation of peripheral blood mononuclear cell metabolism in subjects with type 2 diabetes. URS Thesis 31.|
Abstract: Type 2 diabetes (T2D) is an increasing health concern as 425 million people are diagnosed with it worldwide. It is associated with chronic systemic inflammation and increased oxidative stress; individuals with these inflammatory conditions have altered metabolic pathways and mitochondrial function including changes in mitochondrial respiration values in peripheral blood mononuclear cells (PBMCs). Mitochondrial respiratory capacity is vital to produce cellular energy in the form of adenosine triphosphate (ATP) via the tricarboxylic acid (TCA) cycle and mitochondrial electron transport chain (ETC). Metabolic dysfunction associated with systemic inflammation can lead to limited production of tricarboxylic acid (TCA) cycle intermediates which are vital for metabolism. It has previously been shown that providing anaplerotic TCA cycle precursors, specifically isoleucine and valine, can replenish TCA cycle intermediates. The purpose of this study was to assess the mitochondrial function in PBMCs from eight control subjects and seven T2D subjects using high resolution respirometry. Subjects with T2D received ten days of treatment with three grams daily of supplemental isoleucine. PBMC respiration was compared between control and T2D at baseline, and T2D subjects were assessed for changes over the treatment duration. Subjects with T2D had significantly lower leak respiration and leak-related coupling control ratio than healthy control subjects. There was no significant change in measures of PBMC respiration from T2D subjects before and after treatment. Although there appears to be minor differences in PBMC respiratory rate between subjects with T2D and healthy controls, 10 days of isoleucine supplementation was not effective at recovering altered PBMC respiration in T2D subjects.
• Keywords: Mitochondria, Respiratory, Type 2 diabetes, Dysfunction, Peripheral blood mononuclear cells, Electron transport chain, Oxidative function • Bioblast editor: Plangger M
Labels: MiParea: Respiration, Patients Pathology: Diabetes
Organism: Human Tissue;cell: Blood cells Preparation: Permeabilized cells, Intact cells
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k