TGR5 as New Target in Diabetes Care

Bile acids (BAs) possess an amphipathic steroid molecule which may facilitate the intestinal absorption, emulsification, and transport of lipophilic nutrients and vitamins. Ba is mainly derived from the catabolism of cholesterol in the liver. Recently, BA has been introduced as the endogenous molecules showing pleiotropic responses [1], including glucose and energy homeostasis [2]. Some BAs scape the enterohepatic cycling to reach the systemic circulation [3]. Thus, they participate the functional processes such as lipid and glucose homeostasis, energy expenditure, intestinal mobility, inflammation [4], configuration, and the growth of gut microbiome or the skeletal muscle mass [5]. Dysregulated signaling of BAs have been indicated to involve in some disorders, including diabetes, obesity, dyslipidemia, fatty liver disease, atherosclerosis, cholestasis, gallstones, and cancer [6]. Basically, these effects of Bas were known to binding with the nuclear hormone farnesoid X receptor (FXR) and Takeda G protein receptor 5 (TGR5) in multiple organs [7]. In clinics, treatment of T2DM patients with the BA-like agent(s), or bariatric surgery in obese patients, results in a marked improvement in glycemic control that seems related with the changes in TGR5 and signaling. Therefore, we focus on the role of TGR5 in glucose homeostasis.