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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Calcium Signaling, Cyclic AMP, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Dose-Response Relationship, Drug, Glucose, In Vitro Techniques, Insulin, Insulin-Secreting Cells, KATP Channels, Male, Mice, Mice, Inbred C57BL, Phosphorylation, Protein Kinase Inhibitors, Receptors, G-Protein-Coupled, Signal Transduction, Taurochenodeoxycholic Acid.
user
Does the bile acid TUDCA increase glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells? Context: 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. 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. 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.
assistant
Our data indicate that TUDCA potentiates GSIS through the cAMP/PKA pathway. Final Decision: yes