In the liver, TUDCA improves insulin sensitivity by reducing endoplasmic reticulum (ER) stress28,29. Also, TUDCA activates insulin signaling in the liver, by the interaction with the sphingosine-1-phosphate receptor 2 (S1PR2), resulting in PI3K/Akt pathway activation30. However, the effect of TUDCA upon insulin clearance, as well as hepatic IDE expression remains unclear.