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

Autor(es)

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]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Dept Struct & Funct Biol, Inst Biol, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, NOV 1 2017.
• Citações Web of Science: 8

Resumo

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)

• Processo FAPESP: 14/01717-9 - Investigação dos efeitos insulinotrópicos, insulinomiméticos e endoteliais da taurina em células/tecidos submetidos à restrição in vitro de aminoácidos: uma abordagem integrada e multifocal
• Beneficiário: Everardo Magalhães Carneiro
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/12611-0 - Mecanismos moleculares envolvidos na disfunção e morte de células beta pancreáticas no Diabetes mellitus: estratégias para a inibição desses processos e para a recuperação da massa insular
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/01318-4 - Caracterização da ação do ácido tauroursodesoxicolico (TUDCA) sobre a função pancreática endócrina e ação do glucagon em tecidos alvo em camundongos ob/ob
• Beneficiário: Jean Franciesco Vettorazzi
• Modalidade de apoio: Bolsas no Brasil - Doutorado