The bile acid TUDCA modulates insulin clearance

Abstract

Obesity and type 2 diabetes affects million peoples around the world, and is characterized by hyperinsulinemia state which impairs many tissues function and insulin action. The hyperinsulinemic is due to enhanced insulin secretion by pancreatic islets and a reduced liver insulin clearance and IDE expression. The Tauroursodeoxycholic acid is secreted mainly after meal ingestion and have an important function in digestion. Previous studies have been demonstrated that TUDCA improves glucose tolerance, insulin sensitivity and insulin secretion in insulin resistant models. However the effect of this bile acid on insulin clearance have not been explored yet. Here, we acessed insulin clearance and liver IDE expression in C57BL6 mice fed high fat diet (HFD) and treated with TUDCA (HFD + TUDCA). As expected the mice fed on HFD presents impaired glucose tolerance, insulin sensitivity, and increased insulinemia and c-peptide, and reduction in insulin clearance and IDE expression. The impairments of HFD upon glucose tolerance, insulin sensitivity, and insulin clearance were improved by TUDCA administration. Interestingly, the reestablishment of insulinemia in HFD + TUDCA was associated with an augmented IDE expression on liver. So, we conclude that the bile acid TUDCA, in addition to regulates insulin secretion and signaling in HFD fed mice, also recovery the plasma insulin levels probably due to an increased in IDE expression in the liver which also may contributes to the improvement of glucose homeostasis.