Differential effects of metformin on bile salt absorption from the jejunum and ileum
Differential effects of metformin on bile salt absorption from the jejunum and ileum
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DOI：
10.1046/j.1463-1326.2003.00252.x
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发表时间：
2003-03-01
影响因子：
5.8
通讯作者：
Bailey, CJ
中科院分区：
文献类型：
--
作者：
Carter, D;Howlett, HCS;Bailey, CJ
目的：抗糖尿病药物二甲双胍通常与总循环胆固醇的小幅降低有关，但其机制尚不清楚。由于胆盐对胆固醇稳态有重要作用，本研究研究探讨了二甲双胍对空肠和回肠吸收胆盐的影响，以及它们向胆汁中的转移。方法：将[1-C-14]-甘胆酸钠（250 mg/kg）注入麻醉大鼠的空肠或回肠中，加入或不加入二甲双胍。血浆和胆汁中的C-14-甘氨胆酸盐的出现，随后为150 min。结果：C-14-甘氨胆酸盐从回肠的吸收，这是一个高容量的主动过程，是10倍大于从空肠的吸收，这主要是一个被动的过程。二甲双胍使空肠中C-14-甘胆酸的吸收增加了3倍。二甲双胍同样增加了血浆和胆汁中空肠（14）C-甘胆酸盐的出现。与空肠相反，二甲双胍抑制回肠中C-14-甘胆酸盐的吸收超过一半。这与血浆和bile.Discussion中C-14-甘胆酸盐的相应减少有关：因此，二甲双胍诱导了回肠对主动胆盐吸收的大量抑制，而空肠的被动吸收略有增加。这表明二甲双胍降低总体胆盐吸收的回肠作用可能有助于该药物的适度降胆固醇作用。
Aims: The antidiabetic drug metformin is often associated with a small reduction in total circulating cholesterol, but the mechanism responsible is unknown. As bile salts contribute significantly to cholesterol homeostasis, this study has investigated the effect of metformin on the absorption of bile salts by the jejunum and ileum, and their transfer into bile.Methods: Sodium-[1-C-14]-glycocholate was administered into the jejunum or ileum of anaesthetized rats with and without metformin (250 mg/kg). Appearance of C-14-glycocholate in plasma and bile was followed for 150 min.Results: Absorption of C-14-glycocholate from the ileum, which is a high-capacity active process, was 10-fold greater than absorption from the jejunum, which is mainly a passive process. Metformin increased threefold the absorption of C-14-glycocholate from the jejunum. Metformin similarly increased the appearance of jejunal (14) C-glycocholate in plasma and bile. In contrast to the jejunum, absorption of C-14-glycocholate from the ileum was suppressed by more than half with metformin. This was associated with corresponding reductions of C-14-glycocholate in plasma and bile.Discussion: Thus, metformin induced a large suppression of active bile salt absorption from the ileum compared with a small increase in passive absorption from the jejunum. This suggests that the ileal effect of metformin to reduce overall bile salt absorption could contribute to the modest cholesterol-lowering effect of this drug.