This uncommissioned review article was subject to full peer-review.
Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease
Article first published online: 11 OCT 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 36, Issue 10, pages 909–921, November 2012
How to Cite
Zarrinpar, A. and Loomba, R. (2012), Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease. Alimentary Pharmacology & Therapeutics, 36: 909–921. doi: 10.1111/apt.12084
- Issue published online: 16 OCT 2012
- Article first published online: 11 OCT 2012
- Accepted manuscript online: 12 OCT 2012 12:00AM EST
- Manuscript Accepted: 22 SEP 2012
- Manuscript Revised: 20 AUG 2012
- Manuscript Revised: 27 JUN 2012
- Manuscript Received: 1 JUN 2012
- National Institutes of Health
- Daiichi Sankyo, Inc. Grant Number: T32 DK07202
- American Gastroenterological Association
- Atlantic Philanthropies, Inc. Grant Number: K23 DK090303
Recent research has led to an interest in the role of the gut and liver in type 2 diabetes mellitus (T2DM).
To review the role of the gastrointestinal system in glucose homoeostasis, with particular focus on the effects of incretin hormones, hepatic steatosis and bile acids.
PubMed and Google Scholar were searched using terms such as incretin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase-4 (DPP-4), hepatic steatosis, bile acid and gastric bypass. Additional relevant references were identified by reviewing the reference lists of articles.
Perturbations of incretin hormones and bile acid secretion contribute to the pathogenesis of T2DM, leading to their potential as therapeutic targets. The incretin hormones (GIP and GLP-1) are deactivated by DPP-4. GLP-1 agonists and DPP-4 inhibitors improve glycaemic control in patients with T2DM. Hepatic steatosis, along with insulin resistance, may precede the development of T2DM, and may benefit from anti-diabetes medications. Bile acids play an important role in glucose homoeostasis, with effects mediated via the farnesoid X receptor (FXR) and the cell surface receptor TGR5. The bile acid sequestrant colesevelam has been shown to be effective in improving glycaemic control in patients with T2DM. Altered gastrointestinal anatomy after gastric bypass surgery may also affect enterohepatic recirculation of bile acids and contribute to improved glycaemic control.
Research in recent years has led to new pathways and processes with a role in glucose homoeostasis, and new therapeutic targets and options for type 2 diabetes mellitus.