This thesis examined aspects of production and utilization of acetate in humans via measurements of plasma concentrations in different circumstances with particular attention to changes in diabetes. Circulating plasma acetate was measured by a modified acetate kinase-based enzymatic spectrophotometric method with adequate sensitivity and specificity for levels encountered in human plasma. Fasting plasma acetate was increased in diabetics and correlated with glucose and indices of glucose disposal. Levels increased further when they were fed different high- fibre diets. The rise in acetate levels after lactulose ingestion correlated with changing breath hydrogen excretion in subjects with suspected malabsorption. Plasma acetate levels increased during fat infusion, and conversely, fell with suppression of fatty acid levels during euglycaemic clamping. Insulin appeared to promote acetate production from glucose by enhancing glycolysis and acetyl CoA availability, although its activity in reducing lipolysis had an opposite effect. The hepatic formation of acetate from ethanol did not appear influenced by prior chlorpropamide intake. Glucose tolerance was unaffected by a 150mmol/hr acetate load, but acetate tolerance was impaired when glucose was simultaneously available. Adipose tissue lipolysis was suppressed during acetate infusions as evident from reduced levels of glycerol and non-esterifled fatty acids. Blood 'ketone body' levels were increased, suggesting direct conversion from acetate. Possibly as a result, fat oxidation assessed from gaseous exchange, was reduced with infused acetate. Acetate utilization was impaired in diabetic patients from higher fasting plasma levels and slower metabolic clearance. The defect in diabetes was probably due to both over-production and under-utilization, and could be related to the enhanced lipolysis, hyperglycaemia and a reportedly reduced hepatic activity of acetyl CoA synthetase. It was concluded that acetate is derived from both colonic fermentation and endogenous catabolism of glucose and fatty acids and appears rapidly metabolisable in humans. Some areas of further interest in human acetate metabolism were highlighted.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:670387 |
| Date | January 1987 |
| Creators | Akanji, Abayomi Olusola |
| Contributors | Hockaday, Derek |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:977874a3-523c-4428-8900-248e2786219f |
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