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

Starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation in rats treated with the α-glucosidase inhibitor acarbose
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DOI:
10.1079/bjn20031063
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发表时间:
2004-03-01
影响因子:
3.6
通讯作者:
Mathers, JC
Mathers, JC
中科院分区:
医学3区
文献类型:
--
作者:
Dehghan-Kooshkghazi, M;Mathers, JC

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阿卡波糖(GLucobay@;拜耳)是一种用于治疗糖尿病的α-葡萄糖苷酶抑制剂,可能在预防2型糖尿病方面具有作用。本研究探讨了阿卡波糖处理对淀粉消化部位和程度、大肠发酵和肠粘膜细胞增殖的影响。18只年轻的雄性Wistar大鼠被喂以含有阿卡波糖0、250和500毫克/公斤(6只/只)的“西化”饮食21d。在大多数测量变量中,两种阿卡波糖剂量都有相似的效果。阿卡波糖处理抑制了小肠中的淀粉消化,但通过大肠中的细菌发酵进行了补偿挽救。伴随而来的是小肠和大肠组织的显著肥大,以及沿着肠道的隐窝宽度的持续增加。盲肠总SCFA池大小增加了4倍多,丁酸盐的增加更大。丁酸盐的这些变化反映在门静脉和心脏血液中丁酸盐摩尔比例的增加。阿卡波糖对隐窝细胞增殖无明显影响(仅对中、小肠者有明显促进作用)。这是对增加发酵和丁酸供应增加促进肠粘膜细胞增殖的假设的有力证据。总而言之,除了增加粪便中的淀粉损失外,没有证据表明阿卡波糖对大肠功能方面有不良影响。
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.