Abstract
AimsPancreatic 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 MethodsmRNA 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.ResultsWe 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.ConclusionsOur results indicate that prolonged Htr2b activation in murine β-cells decreases glucose-stimulated insulin secretion and mitochondrial activity by mechanisms likely dependent on enhanced PGC1α/PPARy expression.
Highlights
Most studies on serotonin (5-hydroxytryptamine, 5HT) focus on its role as a central neurotransmitter, the bulk of 5HT (>90%) is synthetized by enteroendocrine cells, secreted to systemic circulation and stored in platelets [1]
We found that mRNA levels of most 5HT receptors were either very low or undetectable in MIN6 cells
Preincubation (6 h) of MIN6 cells with 5HT or BW723C86 reduced glucose-stimulated insulin secretion (GSIS) and the effect of 5HT was prevented by SB204741
Summary
Most studies on serotonin (5-hydroxytryptamine, 5HT) focus on its role as a central neurotransmitter, the bulk of 5HT (>90%) is synthetized by enteroendocrine cells, secreted to systemic circulation and stored in platelets [1]. Additional peripheral tissues are able to synthesize and release small amounts of 5HT [1, 2]. These microserotoninergic systems have been involved in auto and paracrine regulatory circuits. Pancreatic β-cells are recognized as a bona fide microserotonergic system, able to synthesize, store and release 5HT in response to glucose stimulation [3,4,5,6]. By contrast, prolonged exposure of pancreatic β-cells and murine islets to 5HT decreases GSIS [11, 12]. Htr2b receptor mediates insulin opposite actions of gut-derived 5HT in adipocytes and hepatocytes [14, 15], the role of Htr2b in β-cells regulating GSIS has been poorly studied
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