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Differential effects of metformin on bile salt absorption from the jejunum and ileum
Author(s) -
Carter D.,
Howlett H. C. S.,
Wiernsperger N. F.,
Bailey C. J.
Publication year - 2003
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.2003.00252.x
Subject(s) - jejunum , ileum , medicine , metformin , absorption (acoustics) , chemistry , endocrinology , materials science , insulin , composite material
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‐ 14 C]‐glycocholate was administered into the jejunum or ileum of anaesthetized rats with and without metformin (250 mg/kg). Appearance of 14 C‐glycocholate in plasma and bile was followed for 150 min. Results: Absorption of 14 C‐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 14 C‐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 14 C‐glycocholate from the ileum was suppressed by more than half with metformin. This was associated with corresponding reductions of 14 C‐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.