Starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation in rats treated with the alpha-glucosidase inhibitor acarbose.
Acarbose (Glucobay; Bayer) is an alpha-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 500 mg acarbose/kg (six rats/diet) for 21 d. 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.
Human Nutrition Research Centre, School of Clinical Medical Sciences, University of Newcastle, Newcastle-upon-Tyne NE1 7RU, UK.
Mahshid
M
Dehghan-Kooshkghazi
John C
JC
Mathers
D020909:Acarbose / Q000494:pharmacology*; D000818:Animals; D002432:Cecum / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004063:Digestion / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005285:Fermentation / Q000187:drug effects* / Q000502:physiology; D065089:Glycoside Hydrolase Inhibitors; D006128:Growth / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013213:Starch / Q000378:metabolism*
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D013213:Starch; D020909:Acarbose