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Metabolism. 2016 Mar;65(3):54-63. doi: 10.1016/j.metabol.2015.10.021. Epub 2015 Oct 17.

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

Author information

1
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil; Institute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Miguel Hernández University, 03202, Elche, Spain.
2
Integrated Laboratory of Morphology, Centre for Ecology and Socio-Environmental - NUPEM, Federal University of Rio de Janeiro (UFRJ), Macaé, Rio de Janeiro, Brazil.
3
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil.
4
Department of Physiology, Genetics and Microbiology, University of Alicante, 03080 Alicante, Spain.
5
Institute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Miguel Hernández University, 03202, Elche, Spain.
6
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil. Electronic address: emc@unicamp.br.

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.

KEYWORDS:

Bile acids; Insulin secretion; TUDCA; β-cell

PMID:
26892516
DOI:
10.1016/j.metabol.2015.10.021
[Indexed for MEDLINE]

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