Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-27T13:33:43.715Z Has data issue: false hasContentIssue false
  • English
  • Français

Starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation in rats treated with the α-glucosidase inhibitor acarbose

Published online by Cambridge University Press:  09 March 2007

Mahshid Dehghan-Kooshkghazi  and
John C. Mathers
Mahshid Dehghan-Kooshkghazi
Affiliation:
Human Nutrition Research Centre, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK Population Health Research Center, McMaster University, Hamilton, Ontario, Canada
John C. Mathers*
Affiliation:
Human Nutrition Research Centre, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
*
*Corresponding author: Professor John Mathers, fax +44 191 222 8684, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Acarbose (Glucobay®; Bayer) is an α-glucosidase inhibitor used to treat diabetes and which may have a role in the prevention of type 2 diabetes. The present study investigated the effects of acarbose treatment on the site and extent of starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation. Eighteen young male Wistar rats were fed ‘Westernised’ diets containing 0, 250 and 500mg acarbose/kg (six rats/diet) for 21d. For most variables measured, both acarbose doses had similar effects. Acarbose treatment suppressed starch digestion in the small bowel but there was compensatory salvage by bacterial fermentation in the large bowel. This was accompanied by a substantial hypertrophy of small- and large-bowel tissue and a consistent increase in crypt width along the intestine. Caecal total SCFA pool size was increased more than 4-fold, with even bigger increases for butyrate. These changes in butyrate were reflected in increased molar proportions of butyrate in blood from both the portal vein and heart. There was little effect of acarbose administration on crypt-cell proliferation (significant increase for mid-small intestine only). This is strong evidence against the hypothesis that increased fermentation and increased supply of butyrate enhances intestinal mucosal cell proliferation. In conclusion, apart from the increased faecal loss of starch, there was no evidence of adverse effects of acarbose on the aspects of large-bowel function investigated.

Keywords

AcarboseStarch digestionButyrateCrypt widthCell proliferation
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 3 , March 2004 , pp. 357 - 365
Copyright
Copyright © The Nutrition Society 2004

References

Ardawi, MSM & Newsholme, EA (1985) Fuel utilization in colonocytes of the rat. Biochem J 231, 713–719.CrossRefGoogle ScholarPubMed
Bischoff, H (1994) Pharmacology of α-glucosidase inhibition. Eur J Clin Invest 24, Suppl. 3, 3–10.Google ScholarPubMed
Calvert, RJ, Otsuka, M & Satchithanandam, S (1989) Consumption of raw potato starch alters intestinal function and colonic cell proliferation in the rat. J Nutr 119, 1610–1616.CrossRefGoogle ScholarPubMed
Chiasson, JL, Gomis, R, Hanefeld, M, Josse, RG, Karasik, A & Laakso, M (1998) The STOP-NIDDM trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose intolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus. Diabetes Care 21, 1720–1725.CrossRefGoogle Scholar
Chiasson, JL, Josse, RG, Gomis, R, Hanefeld, M, Karasik, & Laakso, M; STOP-NIDDM Trial Research Group(2002) Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359, 2072–2077.CrossRefGoogle ScholarPubMed
Coniff, RF, Shapiro, JA & Seaton, TB (1994) Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin dependent diabetes mellitus. Arch Intern Med 154, 2442–2448.CrossRefGoogle ScholarPubMed
Couet, C, Ulmer, M, Hamdaoui, M, Bau, HM & Debry, G (1989) Metabolic effects of acarbose in young healthy men. Eur J Clin Nutr 43, 187–196.Google ScholarPubMed
Cummings, JH, Beatty, ER, Kingman, SM, Bingham, SA & Englyst, HN (1996) Digestion and physiological properties of resistant starch in the human large bowel. Br J Nutr 75, 733–747.CrossRefGoogle ScholarPubMed
Demigné, C, Yacoub, C & Rémésy, C (1986) Effects of absorption of large amounts of volatile fatty acids on rat liver metabolism. J Nutr 116, 77–86.CrossRefGoogle ScholarPubMed
Deschner, E, Lewis, CM & Lipkin, M (1963) In vitro study of human rectal epithelial cells. 1. Atypical zone of H3 thymidine incorporation in mucosa of multiple polyposis. J Clin Invest 42, 1922–1928.CrossRefGoogle Scholar
Dimitriadis, GD, Tessari, P, Go, VLW & Gerich, JE (1985) α-Glucosidase inhibition improves postprandial hyperglycemia and decreases insulin requirements in insulin-dependent diabetes mellitus. Metabolism 34, 261–265.CrossRefGoogle ScholarPubMed
Englyst, HN & Cummings, JH (1988) Improved methods for the measurement of dietary fibre as non-starch polysaccharides in plant foods. J Assoc Anal Chem 71, 808–814.Google ScholarPubMed
Englyst, HN, Hay, S & Macfarlane, GT (1987) Polysaccharide breakdown by mixed populations of human faecal bacteria. FEMS Microbiol Lett 45, 163–171.CrossRefGoogle Scholar
Goodlad, JS & Mathers, JC (1988) Effect of food carbohydrates on large intestinal fermentation in vitro. Proc Nutr Soc 47, 176A.Google Scholar
Goodlad, JS & Mathers, JC (1990) Large bowel fermentation in rats given diets containing raw peas (Pisum sativum). Br J Nutr 64, 569–587.CrossRefGoogle ScholarPubMed
Goodlad, JS & Mathers, JC (1991) Digestion by pigs of non-starch polysaccharides in wheat and raw peas (Pisum sativum) fed in mixed diets. Br J Nutr 65, 259–270.CrossRefGoogle ScholarPubMed
Goodlad, RA, Lenton, W, Ghatei, MA, Adrian, TE, Bloom, SR & Wright, NA (1987) Effects of an elemental diet, inert bulk and different types of dietary fibre on the response of the intestinal epithelium to refeeding in the rat and relationship to plasma gastrin, enteroglucagon, and PYY concentrations. Gut 28, 171–180.CrossRefGoogle ScholarPubMed
Goodlad, RA & Wright, NA (1982) Quantitative studies on epithelial replacement in the gut. In Techniques in the Life Sciences. Digestive Physiology, pp. 212/1–212/13 [Titchen, DA, editor]. Limerick, Republic of Ireland: Elsevier Scientific Publishers Ireland Ltd.Google Scholar
Green, SE, Chapman, P, Burn, J, Burt, AD, Bennett, M, Appleton, DR, Varma, JS & Mathers, JC (1998) Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer. Gut 43, 85–92.CrossRefGoogle ScholarPubMed
Hauner, H (1999) The impact of pharmacotherapy on weight management in type 2 diabetes. Int J Obes Relat Metab Disord 23, Suppl. 7, S12–S17.CrossRefGoogle ScholarPubMed
Holman, RR, Cull, CA & Turner, RC (1999) A randomised double-blind trial of acarbose in type 2 diabetes shows improved glycaemic control over 3 years (U.K. Prospective Diabetes Study 44). Diabetes Care 22, 960–964.CrossRefGoogle ScholarPubMed
Holt, PR, Atillasoy, E, Lindenbaum, J, Ho, SB, Lupton, JR, McMahon, D & Moss, SF (1996) Effects of acarbose on fecal nutrients, colonic pH, and short-chain fatty acids and rectal proliferative indices. Metabolism 45, 1179–1187.CrossRefGoogle ScholarPubMed
Johnson, IT, Gee, JM & Brown, JC (1988) Plasma enteroglucagon and small bowel cytokinetics in rats fed soluble non-starch polysaccharides. Am J Clin Nutr 47, 1004–1009.CrossRefGoogle Scholar
Kast, RE (2002) Acarbose related diarrhea: increased butyrate upregulates prostaglandin E. Inflam Res 51, 117–118.CrossRefGoogle ScholarPubMed
Kelloff, GJ, Boone, CW, Steele, VE, Crowell, JA, Lubet, R & Sigman, CC (1994) Progress in cancer chemoprevention: perspectives on agent selection and short-term clinical intervention trials. Cancer Res 54, 2015s–2024s.Google ScholarPubMed
Key, FB, McClean, D & Mathers, JC (1996) Tissue hypertrophy and epithelial proliferation rate in the gut of rats fed on bread and haricot beans (Phaseolus vulgaris). Br J Nutr 76, 273–286.CrossRefGoogle ScholarPubMed
Key, FB & Mathers, JC (1993) Gastrointestinal responses of rats fed on white and wholemeal breads: complex carbohydrate digestibility and the influence of dietary fat content. Br J Nutr 69, 481–495.CrossRefGoogle ScholarPubMed
Kooshkghazi, MD & Mathers, JC (1998) Acarbose increases caecal short-chain fatty acids (SCFA) and uptake into portal vein. Proc Nutr Soc 57, 43A.Google Scholar
Laube, H, Linn, T & Heyen, P (1998) The effect of acarbose on insulin sensitivity and proinsulin in overweight subjects with impaired glucose tolerance. Exp Clin Endocrinol Diabetes 106, 231–233.CrossRefGoogle ScholarPubMed
Lipkin, M (1974) Phase 1 and phase 2 proliferative lesions of colonic epithelial cells in diseases leading to colonic cancer. Cancer 34, 878–888.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Macfarlane, GT (1991) Fermentation reactions in the large intestine. In Short Chain Fatty Acids: Metabolism and Clinical Importance, Report of the Tenth Ross Research Conference on Medical Issues, pp. 5–10 [Roche, AF, editor]. Columbus, OH: Ross Laboratories.Google Scholar
McNeil, NI, Cummings, JH & James, WPT (1978) SCFA absorption from the human large intestine. Gut 19, 819–822.CrossRefGoogle Scholar
Mallett, AK, Bearne, CA, Young, PJ, Rowland, IR & Berry, C (1988) Influences of starches of low digestibility on the rat caecal microflora. Br J Nutr 60, 597–604.CrossRefGoogle ScholarPubMed
Mathers, JC & Dawson, LD (1991) Large bowel fermentation in rats eating processed potatoes. Br J Nutr 66, 313–329.CrossRefGoogle ScholarPubMed
Mathers, JC, Fernandez, F, Hill, MJ, McCarthy, PT, Shearer, MJ & Oxley, A (1990) Dietary modification of potential vitamin K supply from enteric bacterial menaquinones in rats. Br J Nutr 63, 639–652.CrossRefGoogle ScholarPubMed
Mathers, JC & Goodlad, JS (1999) Carbohydrate fermentation and microbial cell growth in suspensions of pig large bowel contents. Sci Aliments 19, 491–497.Google Scholar
Mathers, JC, Lawlor, PA & Parker, DS (1992) Effects of guar gum supplementation on small intestinal hydrolases in the rat. Proc Nutr Soc 51, 2A.Google Scholar
Mathers, JC, Smith, H & Carter, S (1997) Dose–response effects of raw potato starch on small-intestinal escape, large bowel fermentation and gut transit time. Br J Nutr 78, 1015–1029.CrossRefGoogle ScholarPubMed
Miazza, BM, Al-Mukhtar, MYT, Salmeron, M, Ghatei, MA, Felce-Dachez, M, Filali, A, Villet, R, Wright, NA, Bloom, SR & Crambaud, JC (1985) Hyperenteroglucagonaemia and small intestinal mucosa growth after colonic perfusion of glucose in rats. Gut 26, 518–524.CrossRefGoogle ScholarPubMed
Mills, SJ, Mathers, JC, Chapman, PD, Burn, J & Gunn, A (2001) Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis. Gut 48, 41–46.CrossRefGoogle ScholarPubMed
Mills, SJ, Shepperd, NA, Hall, PA, Hastings, A, Mathers, JC & Gunn, A (1995) Proliferative compartment deregulation in the non-neoplastic colonic epithelium of familial adenomatous polyposis. Gut 36, 391–394.CrossRefGoogle ScholarPubMed
Preston-Martin, S, Pike, MC, Ross, RK, Jones, PA & Henderson, BE (1990) Increased cell division as a cause of human cancer. Cancer Res 50, 7415–7421.Google ScholarPubMed
Quesada, CF, Kimata, H, Mori, M, Nishimura, M, Tsuneyoshi, T & Baba, S (1998) Piroxicam and acarbose as chemopreventive agents for spontaneous intestinal adenomas in APC gene 1309 knockout mice. Jap J Cancer Res 89, 392–396.CrossRefGoogle ScholarPubMed
Roediger, WEW (1980) Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa of man. Gut 21, 793–798.CrossRefGoogle ScholarPubMed
Roediger, WEW (1982) Utilization of nutrients by the isolated epithelial cells of the rat colon. Gastroenterology 83, 424–429.CrossRefGoogle ScholarPubMed
Ruppin, H, Bar-Meir, S, Soergel, KH & Schmitt, MG (1980) Absorption of SCFA by the colon. Gastroenterology 78, 1500–1507.CrossRefGoogle ScholarPubMed
Sakata, T (1987) Stimulatory effects of short-chain fatty acids on epithelial cell proliferation in the rat intestine: a possible explanation for the trophic effects of fermentable fibre, gut microbes and luminal trophic factors. Br J Nutr 58, 95–103.CrossRefGoogle ScholarPubMed
Scheppach, W, Fabian, C, Sachs, M & Kasper, H (1988) The effect of starch malabsorption on fecal short-chain fatty acid excretion in man. Scand J Gastroenterol 23, 755–759.CrossRefGoogle ScholarPubMed
Terpstra, OT, Van Blankenstein, M, Dees, J & Eilers, GAM (1987) Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. Gastroenterology 92, 704–708.CrossRefGoogle ScholarPubMed
Weaver, GA, Krause, JA, Miller, TL & Wolin, MJ (1992) Cornstarch fermentation by the colonic microbial community yields more butyrate than does cabbage fibre fermentation; cornstarch fermentation rates correlate negatively with methanogenesis. Am J Clin Nutr 55, 70–77.CrossRefGoogle ScholarPubMed
Weaver, GA, Tangel, CT, Krause, JA, Parfitt, MM, Jenkins, PL, Rader, JM, Lewis, BA, Miller, TL & Wolin, MJ (1997) Acarbose enhances human colonic butyrate production. J Nutr 127, 717–723.CrossRefGoogle ScholarPubMed
Weaver, GA, Tangel, CT, Krause, JA et al. (2000) Biomarkers of human colonic cell growth are influenced differently by a history of colonic neoplasia and the consumption of acarbose. J Nutr 130, 2718–2725.CrossRefGoogle ScholarPubMed
Williams, EA, Coxhead, JM & Mathers, JC (2003) Anti-cancer effects of butyrate: use of micro-array technology to investigate mechanisms. Proc Nutr Soc 62, 107–115.CrossRefGoogle ScholarPubMed
Wolever, TMS & Chiasson, J-L (2000) Acarbose raises serum butyrate in human subjects with impaired glucose tolerance. Br J Nutr 84, 57–61.CrossRefGoogle ScholarPubMed
Wolin, MJ, Miller, TL, Yerry, S, Zhang, Y, Bank, S & Weaver, GA (1999) Changes in fermentation pathways of fecal microbial communities associated with a drug treatment that increases dietary starch in the human colon. Appl Environ Microbiol 65, 2807–2812.CrossRefGoogle ScholarPubMed