Prolonged Activation of the Htr2b Serotonin Receptor Impairs Glucose Stimulated Insulin Secretion and Mitochondrial Function in MIN6 Cells

Luis Rodrigo Cataldo, María L. Mizgier, Roberto Bravo Sagua, Fabián Jaña, César Cárdenas, Paola Llanos, Dolores Busso, Pablo Olmos, José E. Galgani, José L. Santos, Víctor A. Cortés

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Aims Pancreatic β-cells synthesize and release serotonin (5 hydroxytryptamine, 5HT); however, the role of 5HT receptors on glucose stimulated insulin secretion (GSIS) and the mechanisms mediating this function is not fully understood. The aims of this study were to determine the expression profile of 5HT receptors in murine MIN6 β-cells and to examine the effects of pharmacological activation of 5HT receptor Htr2b on GSIS and mitochondrial function. Materials and Methods mRNA levels of 5HT receptors in MIN6 cells were quantified by RT qPCR. GSIS was assessed in MIN6 cells in response to global serotonergic activation with 5HT and pharmacological Htr2b activation or inhibition with BW723C86 or SB204741, respectively. In response to Htr2b activation also was evaluated the mRNA and protein levels of PGC1α and PPARy by RT-qPCR and western blotting and mitochondrial function by oxygen consumption rate (OCR) and ATP cellular content. Results We found that mRNA levels of most 5HT receptors were either very low or undetectable in MIN6 cells. By contrast, Htr2b mRNA was present at moderate levels in these cells. Preincubation (6 h) of MIN6 cells with 5HT or BW723C86 reduced GSIS and the effect of 5HT was prevented by SB204741. Preincubation with BW723C86 increased PGC1α and PPARy mRNA and protein levels and decreased mitochondrial respiration and ATP content in MIN6 cells. Conclusions Our results indicate that prolonged Htr2b activation in murine β-cells decreases glucosestimulated insulin secretion and mitochondrial activity by mechanisms likely dependent on enhanced PGC1α/PPARy expression.

Original languageEnglish
Article numbere0170213
JournalPLoS ONE
Volume12
Issue number1
DOIs
StatePublished - Jan 2017
Externally publishedYes

Bibliographical note

Funding Information:
This research was funded by "Fondo Nacional de Desarrollo Cient?fico y Tecnol?gico" grants; 1141134 (VC), 1120586 (JLS), 1120443 (CC), 1160332 (CC), 1130217 (JEG). "Fondo de financiamiento de Centros de Investigaci?n en ?reas Prioritarias" grant 15150012 (CC). "Comisi?n Nacional de Investigaci?n en Ciencia y Tecnolog?a"; doctoral scholarship 21140087 (LRC), postdoctoral fellowship 3160226 (RBS), postdoctoral fellowship 3140458 (FJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2017 Cataldo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fingerprint

Dive into the research topics of 'Prolonged Activation of the Htr2b Serotonin Receptor Impairs Glucose Stimulated Insulin Secretion and Mitochondrial Function in MIN6 Cells'. Together they form a unique fingerprint.

Cite this