Effects of Taurocholic Acid on Glycemic, Glucagon-like Peptide-1, and Insulin Responses to Small Intestinal Glucose Infusion in Healthy Humans

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 4; pp. E718 - E722
• Main Authors: Wu, Tongzhi, Bound, Michelle J., Standfield, Scott D., Jones, Karen L., Horowitz, Michael, Rayner, Christopher K.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.04.2013; Copyright by The Endocrine Society
• Subjects: Adult; Bile acids; Blindness; Blood glucose; Blood Glucose - drug effects; Blood Glucose - metabolism; C-Peptide - blood; Cholagogues and Choleretics - pharmacology; Diabetes mellitus (non-insulin dependent); Double-Blind Method; Glucagon; Glucagon - blood; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - blood; Glucose; Glucose - administration & dosage; Glucose - pharmacology; Health; Humans; Infusion Pumps; Insulin; Insulin - blood; Insulin - metabolism; Intestine, Small - drug effects; Intestine, Small - metabolism; Male; Peptides; Small intestine; Taurocholic acid; Taurocholic Acid - pharmacology
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2012-3961

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.