TY - JOUR
T1 - Differential effects of metformin on bile salt absorption from the jejunum and ileum
AU - Carter, D.
AU - Howlett, H. C S
AU - Wiernsperger, N. F.
AU - Bailey, Clifford J.
PY - 2003/3/7
Y1 - 2003/3/7
N2 - 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-[1-14C]-glycocholate was administered into the jejunum or ileum of anaesthetized rats with and without metformin (250 mg/kg). Appearance of 14C-glycocholate in plasma and bile was followed for 150 min. Results: Absorption of 14C-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 14C-glycocholate from the jejunum. Metformin similarly increased the appearance of jejunal 14C-glycocholate in plasma and bile. In contrast to the jejunum, absorption of 14C-glycocholate from the ileum was suppressed by more than half with metformin. This was associated with corresponding reductions of 14C-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.
AB - 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-[1-14C]-glycocholate was administered into the jejunum or ileum of anaesthetized rats with and without metformin (250 mg/kg). Appearance of 14C-glycocholate in plasma and bile was followed for 150 min. Results: Absorption of 14C-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 14C-glycocholate from the jejunum. Metformin similarly increased the appearance of jejunal 14C-glycocholate in plasma and bile. In contrast to the jejunum, absorption of 14C-glycocholate from the ileum was suppressed by more than half with metformin. This was associated with corresponding reductions of 14C-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.
KW - Bile salts
KW - Glycocholate
KW - Hepatic bile
KW - Intestinal absorption
KW - Metformin
UR - http://www.scopus.com/inward/record.url?scp=0345268644&partnerID=8YFLogxK
UR - https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1046/j.1463-1326.2003.00252.x
U2 - 10.1046/j.1463-1326.2003.00252.x
DO - 10.1046/j.1463-1326.2003.00252.x
M3 - Article
C2 - 12630937
AN - SCOPUS:0345268644
SN - 1462-8902
VL - 5
SP - 120
EP - 125
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 2
ER -