Cited by 104Pancreatic function and diabetesDiabetes Treatment and ManagementAldose Reductase and Taurine

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

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Vettorazzi, Jean Franciesco, Ribeiro, Rosane Aparecida, Borck, Patricia Cristine, Branco, Renato Chaves Souto, Soriano, Sergi, Merino, Beatriz, Boschero, Antônio Carlos, Nadal, Angel, Quesada, Ivan, Carneiro, Everardo Magalhães·2016·Metabolism

DOI 10.1016/j.metabol.2015.10.021

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Abstract

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, Ca(2+) 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, Ca(2+) 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.

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Authors: Vettorazzi, J. F., Ribeiro, R. A., Borck, P. C., Branco, R. C. S., Soriano, S., Merino, B., Boschero, A. C., Nadal, A., Quesada, I., & Carneiro, E. M.
Affiliations: Universitat de Miguel Hernández d'Elx (ES)
Universidade Federal do Rio de Janeiro (BR)
Universidade Estadual de Campinas (UNICAMP) (BR)
University of Alicante (ES)
Corresponding author: Carneiro, Everardo Magalhães
ORCID: Vettorazzi, Jean Franciesco
Ribeiro, Rosane Aparecida
Branco, Renato Chaves Souto
Soriano, Sergi
Merino, Beatriz
Carneiro, Everardo Magalhães
Venue: Metabolism
Publisher: Elsevier BV
Published: 2016-03
Volume: 65
Issue: 3
Pages: 54-63
ISSN: 0026-0495 (ISSN-L)
DOI: 10.1016/j.metabol.2015.10.021
OpenAlex: W2186068515
Cited by: 104
References: 38
Citations by year: 2026: 7 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 9 · 2021: 10 · 2020: 13 · 2019: 10 · 2018: 7 · 2017: 8 · 2016: 5
FWCI: 6.71
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Metabolism (publishedVersion)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
Repositorio Institucional de la Universidad de Alicante (Universidad de Alicante) (submittedVersion)
Funders: 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)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Spanish Ministerio de Ciencia e Innovación (BFU2013-42789-P, BFU2011-28358)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
Keywords: tauroursodeoxycholic acid, bile acids, glucose-stimulated insulin secretion, pancreatic beta cells, cAMP/PKA signaling, TGR5, G protein-coupled receptors, CREB phosphorylation, pancreatic islets, insulin secretion
MeSH terms: Cyclic AMP, Animals, Dose-Response Relationship, Drug, Glucose, Insulin, Male, Mice, Inbred C57BL, Phosphorylation, Taurochenodeoxycholic Acid, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Calcium Signaling, Receptors, G-Protein-Coupled, Protein Kinase Inhibitors, Insulin-Secreting Cells, Mice, KATP Channels, In Vitro Techniques

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

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