AIMS: In patients with type 2 diabetes, rectal administration of bile acids increases glucagon-like peptide-1 (GLP-1) secretion and reduces plasma glucose. In addition, oral bile acid sequestrants (BASs) reduce blood glucose by an unknown mechanism. In this study we evaluated the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the BAS, colesevelam, instilled into the stomach, on plasma levels of GLP-1, glucose-dependent insulinotropic polypeptide, glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin as well as gastric emptying, gallbladder volume, appetite and food intake.

MATERIALS AND METHODS: On 4 separate days, 9 patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of 1) CDCA; 2) colesevelam, 3) CDCA+colesevelam, or 4) placebo. At baseline and during 180 min following instillation, blood was sampled.

RESULTS: In both patients with type 2 diabetes and healthy control subjects, CDCA elicited an increase in GLP-1 vs. colesevelam, CDCA+colesevelam and placebo, respectively (P < 0.05). The interventions did not affect plasma glucose, insulin or C-peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin:glucose ratio vs. colesevelam, CDCA+colesevelam and placebo in both groups. Compared to colesevelam, CDCA+colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups.

CONCLUSIONS: CDCA increased GLP-1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid-induced activation of TGR5 on L cells increases GLP-1 secretion, which in turn may result in amplification of glucose-stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP-1 secretion in humans.