Review for "Mechanism of glucose lowering by metformin in type 2 diabetes: role of bile acids"

Author(s):  
Francesco Andreozzi
2019 ◽  
Author(s):  
Daniel J Sansome ◽  
Cong Xie ◽  
Simon Veedfald ◽  
Michael Horowitz ◽  
Christopher K Rayner ◽  
...  

2019 ◽  
Vol 22 (2) ◽  
pp. 141-148 ◽  
Author(s):  
Daniel J. Sansome ◽  
Cong Xie ◽  
Simon Veedfald ◽  
Michael Horowitz ◽  
Christopher K. Rayner ◽  
...  

2014 ◽  
Vol 171 (2) ◽  
pp. R47-R65 ◽  
Author(s):  
David P Sonne ◽  
Morten Hansen ◽  
Filip K Knop

Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently – despite elusive mechanisms of action – bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.


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