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Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non‐alcoholic fatty liver disease
Author(s) -
Zarrinpar A.,
Loomba R.
Publication year - 2012
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12084
Subject(s) - incretin , medicine , farnesoid x receptor , bile acid , glucose homeostasis , g protein coupled bile acid receptor , insulin resistance , steatosis , endocrinology , type 2 diabetes mellitus , enterohepatic circulation , fatty liver , hormone , gastric inhibitory polypeptide , diabetes mellitus , type 2 diabetes , disease , glucagon , biology , biochemistry , nuclear receptor , transcription factor , gene
Summary Background Recent research has led to an interest in the role of the gut and liver in type 2 diabetes mellitus ( T 2 DM ). Aim 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. Methods 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. Results Perturbations of incretin hormones and bile acid secretion contribute to the pathogenesis of T 2 DM , 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 T 2 DM . Hepatic steatosis, along with insulin resistance, may precede the development of T 2 DM , 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 TGR 5. The bile acid sequestrant colesevelam has been shown to be effective in improving glycaemic control in patients with T 2 DM . Altered gastrointestinal anatomy after gastric bypass surgery may also affect enterohepatic recirculation of bile acids and contribute to improved glycaemic control. Conclusions 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.