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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Bile acid TUDCA improves insulin clearance by increasing the expression of insulin-degrading enzyme in the liver of obese mice

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Author(s):
Vettorazzi, Jean Franciesco [1] ; Kurauti, Mirian Ayumi [1] ; Soares, Gabriela Moreira [1] ; Borck, Patricia Cristine [1] ; Ferreira, Sandra Mara [1] ; Souto Branco, Renato Chaves [1] ; Lima Michelone, Luciana de Souza [1] ; Boschero, Antonio Carlos [1] ; Costa Junior, Jose Maria [1] ; Carneiro, Everardo Magalhaes [1]
Total Authors: 10
Affiliation:
[1] Univ Campinas UNICAMP, Dept Struct & Funct Biol, Inst Biol, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, NOV 1 2017.
Web of Science Citations: 8
Abstract

Disruption of insulin secretion and clearance both contribute to obesity-induced hyperinsulinemia, though reduced insulin clearance seems to be the main factor. The liver is the major site for insulin degradation, a process mainly coordinated by the insulin-degrading enzyme (IDE). The beneficial effects of taurine conjugated bile acid (TUDCA) on insulin secretion as well as insulin sensitivity have been recently described. However, the possible role of TUDCA in insulin clearance had not yet been explored. Here, we demonstrated that 15 days treatment with TUDCA reestablished plasma insulin to physiological concentrations in high fat diet (HFD) mice, a phenomenon associated with increased insulin clearance and liver IDE expression. TUDCA also increased IDE expression in human hepatic cell line HepG2. This effect was not observed in the presence of an inhibitor of the hepatic membrane bile acid receptor, S1PR2, nor when its downstream proteins were inhibited, including IR, PI3K and Akt. These results indicate that treatment with TUDCA may be helpful to counteract obesity-induced hyperinsulinemia through increasing insulin clearance, likely through enhanced liver IDE expression in a mechanism dependent on S1PR2-Insulin pathway activation. (AU)

FAPESP's process: 14/01717-9 - Investigation of the insulinotropic, insulinomimetic and endothelial actions of taurine in cells/tissues submitted to an in vitro amino acid restriction: an integrated and multifocal approach
Grantee:Everardo Magalhães Carneiro
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass
Grantee:Antonio Carlos Boschiero
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/01318-4 - Characterization of tauroursodesoxicolic (TUDCA) action on the pancreatic endocrine function and action in tissue glucagon target ob / ob mice
Grantee:Jean Franciesco Vettorazzi
Support type: Scholarships in Brazil - Doctorate