Incretin secretion stimulated by ursodeoxycholic acid in healthy subjects.

Bile acids play an important role in post-prandial glucose metabolism by stimulating release of glucagon-like peptide-1 (GLP-1) via the G-protein-coupled receptor TGR5, which is expressed in intestinal L cells. Thus, bile acid sequestrants are expected to stimulate secretion of endogenous GLP-1 through TGR5. We investigated incretin and insulin secretion after a meal with and without ursodeoxycholic acid (UDCA), a widely used therapeutic agent in liver diseases, in 7 non-diabetic Japanese subjects. We found that UDCA intake resulted in higher GLP-1 secretion (area under the curve [AUC] of 0-60 min after meal without UDCA, 450 ± 162 mmol·min/l; with UDCA, 649 ± 232 mmol·min/l, P = 0.046) and lower blood glucose (AUC of 0-60 min without UDCA, 7191 ± 250 mg·min/dl; with UDCA, 6716 ± 189 mg·min/dl, P = 0.001) , although we did not find statistically significant insulin increase by UDCA intake (AUC of 0-60 min without UDCA, 1551 ± 418 μU·min/ml; with UDCA, 1941 ± 246 μU·min/ml, P = 0.065). These results suggest that UDCA increases bile-induced GLP-1 secretion. Ours is the first report showing increased GLP-1 secretion and decreased blood glucose in response to UDCA.