Glucose-lowering effects of intestinal bile acid sequestration through enhancement of splanchnic glucose utilization

Trends Endocrinol Metab. 2014 May;25(5):235-44. doi: 10.1016/j.tem.2014.03.007. Epub 2014 Apr 11.

Abstract

Intestinal bile acid (BA) sequestration efficiently lowers plasma glucose concentrations in type 2 diabetes (T2D) patients. Because BAs act as signaling molecules via receptors, including the G protein-coupled receptor TGR5 and the nuclear receptor FXR (farnesoid X receptor), to regulate glucose homeostasis, BA sequestration, which interrupts the entero-hepatic circulation of BAs, constitutes a plausible action mechanism of BA sequestrants. An increase of intestinal L-cell glucagon-like peptide-1 (GLP-1) secretion upon TGR5 activation is the most commonly proposed mechanism, but recent studies also argue for a direct entero-hepatic action to enhance glucose utilization. We discuss here recent findings on the mechanisms of sequestrant-mediated glucose lowering via an increase of splanchnic glucose utilization through entero-hepatic FXR signaling.

Keywords: FXR; TGR5; bile acid sequestrant; glucose homeostasis; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bile Acids and Salts / metabolism*
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose / metabolism*
  • Homeostasis / physiology
  • Humans
  • Intestinal Mucosa / metabolism*
  • Liver / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction / physiology

Substances

  • Bile Acids and Salts
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Glucagon-Like Peptide 1
  • Glucose