Possible contribution of tauroursodeoxycholic acid (TUDCA) on the remission of type 2 diabetes in mice submitted to Duodenal-Jejunal Bypass

• Grant number: 17/13410-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2017
• End date: July 28, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Jean Franciesco Vettorazzi
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Type 2 diabetes mellitus (T2D) currently affects almost 10% of the global population, accounting for thousands of amputations and deaths. In T2D, there is a failure in the secretion and signaling of insulin, in addition to an increase in the plasma concentration of glucagon, effects that contribute to the establishment of hyperglycemia. Several strategies have been used in the treatment of T2D, among them the surgeries that exclude the initial portion of the small intestine, such as the Duodenal-jejunal bypass (DJB). DJB reverses the effects of T2D on humans and animal models, increasing insulin and reducing glucagon secretion, as well as increasing the concentration of various compounds in plasma such as bile acids. Bile acids are currently recognized as signaling molecules that regulate glycemic, lipid and energy metabolism, and are used in the treatment of T2D. The bile acid TUDCA regulates the secretion of insulin and glucagon, in addition to modulating insulin sensitivity and energy metabolism, and this bile acid is increased after DJB. However, the participation of TUDCA in the reversal of T2D by DJB has not yet been clarified. In this project, we propose to investigate whether the beneficial effects of DJB on glycemic homeostasis are dependent on the effects of TUDCA involved with the secretion / degradation of insulin and glucagon. In addition, we aim to synthesize a nanoparticle associated with TUDCA, which increases its bioavailability and can mimic the effects of DJB.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZANGEROLAMO, LUCAS; VETTORAZZI, JEAN F.; SOLON, CARINA; BRONCZEK, GABRIELA A.; ENGEL, DAIANE F.; KURAUTI, MIRIAN A.; SOARES, GABRIELA M.; RODRIGUES, KARINA S.; VELLOSO, LICIO A.; BOSCHERO, ANTONIO C.; et al. The bile acid TUDCA improves glucose metabolism in streptozotocin-induced Alzheimer's disease mice model. Molecular and Cellular Endocrinology, v. 521, FEB 5 2021. (13/07607-8, 15/12611-0, 17/13410-3, 15/23729-1, 18/06363-1, 18/20213-2)

BRONCZEK, GABRIELA ALVES; VETTORAZZI, JEAN FRANCIESCO; SOARES, GABRIELA MOREIRA; KURAUTI, MIRIAN AYUMI; SANTOS, CRISTIANE; BONFIM, MARESSA FERNANDES; CARNEIRO, EVERARDO MAGALHAES; BALBO, SANDRA LUCINEI; BOSCHERO, ANTONIO CARLOS; COSTA JONIOR, JOSE MARIA. The Bile Acid TUDCA Improves Beta-Cell Mass and Reduces Insulin Degradation in Mice With Early-Stage of Type-1 Diabetes. FRONTIERS IN PHYSIOLOGY, v. 10, MAY 15 2019. (17/13410-3, 15/12611-0)