The relationship between human colonic mucosal metabolism and mucin synthesis was explored, with particular reference to ulcerative colitis (UC) and pouchitis. A hypothesis was proposed, that UC and pouchitis result from impaired metabolism of butyrate, and that the outcome of this metabolic event was reduced mucosal protection via effects on mucin synthesis. The study aims were to assess mucosal metabolism in the ileum and colon in controls and in UC, and to assess the effects of agents that are effective therapy for UC on metabolism as measured by mucin synthesis. In histologically normal colonoscopic mucosal biopsies cultured <I>in vitro</I>, the rate of metabolism of butyrate was similar in the ascending (AC) and descending colon (DC). There was a higher rate of metabolism of glutamine in the ascending colon, in agreement with previous work which stressed the relatively greater dependence of the distal colon on butyrate as an energy source. The terminal ileum (TI), in controls had a surprisingly high rate of metabolism of butyrate, significantly higher than the AC, glutamine metabolism in controls was also greater than in the AC. In ulcerative colitis (UC) the most striking change in epithelial metabolism was an increase in the rate of glutamine metabolism in the descending colon. The rates of butyrate metabolism in UC were similar to those in controls, the ratio of butyrate:glutamine metabolism was non-significantly lower in the descending colon in UC as a result of the increased rate of glutamine metabolism. Rates of metabolism in the terminal ileum were similar in UC and controls. Butyrate, at concentrations that are likely to be physiologically and pharmacologically relevant, significantly increased mucin synthesis in colonic mucosal explants from histologically normal and diseased (UC) tissue. Glucocorticoids and nicotine similarly increased colonic mucin synthesis, whereas mineralocorticoids were without effect.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:342167 |
| Date | January 1996 |
| Creators | Finnie, Ian A. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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