The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells

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Título: The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells
Autor/es: Vettorazzi, Jean Franciesco | Ribeiro, Rosane Aparecida | Borck, Patricia Cristine | Branco, Renato Chaves Souto | Soriano Úbeda, Sergi | Merino, Beatriz | Boschero, Antônio Carlos | Nadal, Ángel | Quesada, Iván | Carneiro, Everardo Magalhães
Grupo/s de investigación o GITE: Fisiología Neuroendocrina (FINE)
Centro, Departamento o Servicio: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Palabras clave: β-cell | Bile acids | Insulin secretion | TUDCA
Área/s de conocimiento: Fisiología
Fecha de publicación: mar-2016
Editor: Elsevier
Cita bibliográfica: Metabolism. 2016, 65(3): 54-63. doi:10.1016/j.metabol.2015.10.021
Resumen: Objective. While bile acids are important for the digestion process, they also act as signaling molecules in many tissues, including the endocrine pancreas, which expresses specific bile acid receptors that regulate several cell functions. In this study, we investigated the effects of the conjugated bile acid TUDCA on glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. Methods. Pancreatic islets were isolated from 90-day-old male mice. Insulin secretion was measured by radioimmunoassay, protein phosphorylation by western blot, Ca2 + signals by fluorescence microscopy and ATP-dependent K+ (KATP) channels by electrophysiology. Results. TUDCA dose-dependently increased GSIS in fresh islets at stimulatory glucose concentrations but remained without effect at low glucose levels. This effect was not associated with changes in glucose metabolism, Ca2 + signals or KATP channel activity; however, it was lost in the presence of a cAMP competitor or a PKA inhibitor. Additionally, PKA and CREB phosphorylation were observed after 1-hour incubation with TUDCA. The potentiation of GSIS was blunted by the Gα stimulatory, G protein subunit-specific inhibitor NF449 and mimicked by the specific TGR5 agonist INT-777, pointing to the involvement of the bile acid G protein-coupled receptor TGR5. Conclusion. Our data indicate that TUDCA potentiates GSIS through the cAMP/PKA pathway.
Patrocinador/es: This work was supported by grants from Fundacão de Amparo á Pesquisa do Estado de São Paulo (FAPESP 2013/01318-4), Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq 200030/2014-0), Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). This study was also supported by grants from the Spanish Ministerio de Ciencia e Innovación (BFU2013-42789-P; BFU2011-28358). CIBERDEM is an initiative of the Instituto de Salud Carlos III.
URI: http://hdl.handle.net/10045/62609
ISSN: 0026-0495 (Print) | 1532-8600 (Online)
DOI: 10.1016/j.metabol.2015.10.021
Idioma: eng
Tipo: info:eu-repo/semantics/article
Derechos: © 2015 Elsevier Inc.
Revisión científica: si
Versión del editor: http://dx.doi.org/10.1016/j.metabol.2015.10.021
Aparece en las colecciones:INV - FINE - Artículos de Revistas

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