Effects of taurocholic acid on glycemic, glucagon-like peptide-1, and insulin responses to small intestinal glucose infusion in healthy humans

J Clin Endocrinol Metab. 2013 Apr;98(4):E718-22. doi: 10.1210/jc.2012-3961. Epub 2013 Feb 15.

Abstract

Context: In vitro and animal studies suggest that bile acids have the capacity to reduce blood glucose by stimulating glucagon-like peptide-1 (GLP-1) and, thereby, insulin.

Objective: This study evaluated the effects of intrajejunal taurocholic acid (TCA) on blood glucose, GLP-1, and insulin responses to jejunal glucose infusion in healthy men.

Participants and design: Ten healthy men were each studied on 2 days in a double-blind, randomized order. After the subjects fasted overnight, a jejunal catheter was positioned and a balloon inflated 30 cm beyond the pylorus with aspiration of endogenous bile. Two grams TCA in saline, or saline control, was infused beyond the balloon over 30 minutes, followed by 2 g TCA or control, together with 60 g glucose, over the next 120 minutes. Blood was sampled frequently for the measurements of blood glucose, total GLP-1, insulin, C-peptide, and glucagon.

Results: Intrajejunal infusion of TCA alone (t = -30 to 0 minutes) had no effect on blood glucose, GLP-1, insulin, C-peptide, or glucagon concentrations. During intrajejunal glucose infusion (t = 0 to 120 minutes), blood glucose concentrations were lower (P < .001), and plasma GLP-1 (P < .001) and the C-peptide/glucose ratio (P = .008) were both greater, whereas plasma insulin, C-peptide, and glucagon levels were not significantly different after TCA than after control.

Conclusions: In healthy humans, small intestinal infusion of TCA potently reduces the glycemic response to small intestinal glucose, associated with an increase in GLP-1 and C-peptide/glucose ratio. These observations indicate the potential for bile acid-based therapy in type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Cholagogues and Choleretics / pharmacology
  • Double-Blind Method
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood*
  • Glucose / administration & dosage*
  • Glucose / pharmacology
  • Health
  • Humans
  • Infusion Pumps
  • Insulin / blood*
  • Insulin / metabolism
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Male
  • Taurocholic Acid / pharmacology*

Substances

  • Blood Glucose
  • C-Peptide
  • Cholagogues and Choleretics
  • Insulin
  • Taurocholic Acid
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose