BA signaling controls the systemic glycemic response. In the liver BA-FXR signaling inhibits gluconeogenesis and promotes glycogen synthesis by negative regulation of PEPCK, G6Pase, and ChREBP. In intestinal L cells, BA-TGR5 signaling leads to GLP-1 expression and secretion, whereas BA-FXR signaling inhibits GLP-1 production. The gut microbiome controls BA diversity, whereas BA composition mediates gut microbiome configuration. In the brain, BA-TGR5 signaling mediates satiety. In skeletal muscles and brown adipose tissue, BA-TGR5 sensing promotes T4 conversion to T3, leading to increased energy expenditure. In the pancreas, both BA-TGR5 and BA-FXR signaling in β cells induces insulin production. Glucose-stimulated insulin release is additionally promoted by BA-TGR5 signaling in α cells, which causes conversion of proglucagon to GLP-1 and GLP-1 release. TGR5-BA in immune cells results in inhibition of NLRP3-inflammasome and attenuated inflammation. CCL, chemokine (C-C motif) ligand; Dio2, type 2 iodothyronine deiodinase; LIP, liver inhibitory protein; T4, thyroxine; T3, tri-iodothyronine.