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

作者：Rodrigo Cataldo Luis; Mizgier Maria L; Bravo Sagua Roberto; Jana Fabian; Cardenas Cesar; Llanos Paola; Busso Dolores; Olmos Pablo; Galgani Jose A E; Santos Jose A L; Cortes Victor A^*

来源：PLos One, 2017, 12(1): e0170213.

DOI：10.1371/journal.pone.0170213

Aims
Pancreatic beta-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 beta-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 PGC1 alpha 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 PGC1a 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 beta-cells decreases glucose-stimulated insulin secretion and mitochondrial activity by mechanisms likely dependent on enhanced PGC1 alpha/PPARy expression.

• 出版日期2017-1-27