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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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Title:
The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells
Authors:
Vettorazzi, Jean Franciesco
Ribeiro, Rosane Aparecida
Borck, Patricia Cristine
Souto Branco, Renato Chaves
Soriano, Sergi
Merino Antolín, Beatriz
Boschero, Antonio Carlos
Nadal Navajas, Ángel
Quesada Moll, Iván
Carneiro, Everardo M.
Department:
Departamentos de la UMH::Biología Aplicada
Issue Date:
2016-03
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, 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.
Keywords/Subjects:
β-cell
Bile acids
Insulin secretion
TUDCA
Type of document:
application/pdf
Access rights:
info:eu-repo/semantics/openAccess
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