The sulfur-containing amino acid, taurine (Tau), regulates glucose and lipid homeostasis under normal, pre- and diabetic conditions. Here, we aimed to verify whether Tau supplementation exerts its beneficial effects against obesity, hyperglycemia and alterations in islet functions, in leptin-deficient obese (ob/ob), over a long period of treatment. From weaning until 12 months of age, female ob/ob mice received, or not, 5% Tau in drinking water (obTau group). After this period, a reduction in hypertriglyceridemia and an improvement in glucose tolerance and insulin sensitivity were observed in obTau mice. In addition, the daily metabolic flexibility was restored in obTau mice. In the gastrocnemius muscle of obTau mice, the activation of AMP-activated protein kinase (AMPK) was increased, while total AMPK protein content was reduced. Finally, isolated islets from obTau mice expressed high amounts of pyruvate carboxylase (PC) protein and lower glucose-induced insulin secretion. Taking these evidences together Tau supplementation had long-term positive actions on glucose tolerance and insulin sensitivity, associated with a reduction in glucose-stimulated insulin secretion, in ob/ob mice. The improvement in insulin actions in obTau mice was due, at least in part, to increased activation of AMPK in skeletal muscle, while the increased content of the PC enzyme in pancreatic islets may help to preserve glucose responsiveness in obTau islets, possibly contributing to islet cell survive.

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.