Some Test about Chenodeoxycholic Acid Colesevelam on Glucagon-like Peptide-1 Secretion

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Gastric Emptying: Indices of gastric emptying are given in Table 1. In both groups, during all four instillations serum paracetamol concentration increased rapidly, indicating a fast gastric emptying of the instilled solutions. Gastric emptying as assessed by paracetamol Tmax was slower after Chenodeoxycholic Acid compared with colesevelam, CDCA+colesevelam and placebo in the healthy control group, and after CDCA compared with colesevelam and placebo in the type 2 diabetes group. Gastric emptying was significantly slower in the healthy control group than in the type 2 diabetes group after Chenodeoxycholic Acid and CDCA+colesevelam (p<0.05). Gallbladder Volume: Gallbladder volumes are shown in Table 1. In both groups, the gallbladder volume iAUC increased slightly after instillation of CDCA compared with colesevelam and CDCA+colesevelam, respectively, and decreased slightly after instillation of colesevelamand CDCA+colesevelam, respectively, compared with placebo. Appetite and Food Intake: No differences in appetite/satiety perceptions or food intake were observed between the different instillations or between the groups.
The present study shows that acute administration of Chenodeoxycholic Acid (1.25 g/32mmol/l) increases plasma GLP-1 and glucagon concentrations, delays gastric emptying and increases gallbladder volume in patients with type 2 diabetes and healthy control subjects. In contrast, acute administration of colesevelam, and CDCAtogether with colesevelam, respectively, did not promote GLP-1 secretion or GLP-1-associated effects. Intraduodenal administration of unconjugated CDCA (2.1 g) increased GLP-1 concentrations without affecting fasting plasma glucose in healthy control subjects. In a cell model, TCA and CDCA (2 μmol/l) similarly activated TGR5. The CDCA-induced increase in GLP-1 secretion observed in the present study was small and similar to that of previous reports, thus, the role of bile acid-induced GLP-1 in human glucose metabolism appears to be small compared with data from animal studies.
In contrast to the studies mentioned above, we used a bolus instillation in the present study and, presumably, achieved a higher local bile acid concentration; however, it is likely that Chenodeoxycholic Acid did not reach the L-cell-rich colon and rectum, and that the affinity of CDCA for TGR5 is too weak (although some CDCA may have reached the colon and been transformed to the secondary and more potent TGR5 agonist lithocholic acid). Indeed, a dose-dependent and greater GLP-1 response along with reduction in plasma glucose after rectal administration of TCA (0.36, 1.08, 3.58 and 10.75 g) in patients with type 2 diabetes,pretreatedwith a single dose of a DPP-4 inhibitor. It did not find evidence of a synergistic effect of administering CDCA and colesevelam together.