High cereal-fiber intake reduces risk of developing type 2 diabetes. Animal studies suggest fiber improves insulin sensitivity via increased GLP-1 secretion stimulated by increased colonic short-chain fatty-acid (SCFA) production. The overall aim of my thesis was to see if these effects occur in humans. The objective of the first study was to determine the time-course of the effects of dietary wheat-fiber on plasma SCFA, GLP-1, glucose, and insulin in hyperinsulinemic humans over 1 year. Subjects (n=28) received either high wheat-fiber (F) (24g fiber/d) (n=14) or low fiber cereal (C) (n=14) daily for 1 yr in a randomized parallel design. Subjects underwent 8-hour metabolic profiles every 3-months. There were no differences in body weight on F vs C. Compared to C, consumption of F significantly increased mean 8-h plasma acetate, butyrate and GLP-1 and significantly reduced fasting glucose, but it took 9 months or more for these effects to become evident (p<0.05).;The results of these experiments suggest that colonic SCFA influence the secretion of GLP-1 and other gut and adipose tissue hormones. However, the metabolic effects of increased cereal-fiber intake may take many months to develop due to adaptation of colonic fermentation and gradual increase in SCFA production.;The objective of the second study was to determine the acute effect of acetate on GLP-1 as well as other gut and adipose hormones. Six hyperinsulinemic females received, in random order, either: 20mmol sodium-acetate intravenously (IVAC); 20mmol normal-saline IV (IVSal); 60mmol sodium-acetate rectally (RAC); or 60mmol normal-saline rectally (RSal). Blood samples were taken fasting and at 10, 15, 30, 45 and 60min after the start of infusion. Plasma GLP-1 and PYY increments were higher after AC than Sal and after R than IV infusion (both p<0.01). TNF-α increments were lower after AC than Sal (p<0.05), but higher after R than IV (p<0.01). Ghrelin increments were higher after R vs IV (p<0.01).
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