Ácido tauroursodesoxicólico (TUDCA) melhora a insulinemia de camundongos com Diabetes do tipo 1 através do aumento da síntese e redução da degradação de insulina

Abstract

Appropriate control of glycaemia in type 1 diabetic patients (T1D) needs daily insulin administration, which can lead to hypoglycemic events and others side effects. Therefore, it is important to find endogenous molecules, without side effects, for T1D treatment. In this sense, the biliary acid conjugated with taurine, tauroursodeoxycholic acid (TUDCA) presents positive effects in type 2 diabetes treatment. However, its beneficial effects on T1D have been less explored. Thus, we have assessed the effects of TUDCA on glycemic control in streptozotocin-induced diabetic mice. For this, C57BL/6 mice received intraperitoneal (i.p.) administration of streptozotocin (40mg/kg, streptozotocin was dissolved in 0,5 M citrate buffer, pH 4,5) for 5 days, STZ group (n=22). Whereas control (CON) group (n=6) received the same volume of citrate buffer. Once confirmed diabetes in the STZ group, diabetic mice were randomly selected and allocated in the 2 following groups: 1) STZ group (n=10) that received i.p. PBS, and 2) STZ+TUDCA group (n=12) that received i.p. 300 mg/kg TUDCA (dissolved in PBS). These treatments were maintained for 24 days. After 15 days of treatment, STZ+TUDCA mice showed a 43% reduction in blood glucose, compared with STZ. This reduction was probably due to an increase in insulinemia. This increase in insulinemia may be explained, at least in part, by a reduction in hepatic activity of IDE (insulin degrading enzyme) the enzyme responsible for insulin degradation, as well as by an increase in beta cell mass and higher beta cell number per islet. All together, these effects contributed to the improvement of metabolic flexibility. In conclusion, TUDCA shows therapeutic potential for the control of glycemia in T1D.