Prolonged Activation of the Htr2b Serotonin Receptor Impairs Glucose Stimulated Insulin Secretion and Mitochondrial

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Luis Rodrigo Cataldo1, María L Mizgier1, Roberto Bravo Sagua2

  • 1Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.

Plos One
|January 28, 2017
PubMed
Abstract

Insights

Prolonged activation of serotonin receptor Htr2b in pancreatic beta cells reduces insulin secretion and mitochondrial function. This occurs through mechanisms involving increased PGC1α/PPARy expression, impacting glucose metabolism.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Pancreatic beta cells synthesize and release serotonin (5-hydroxytryptamine, 5HT).
  • The precise role of 5HT receptors in glucose-stimulated insulin secretion (GSIS) and their underlying mechanisms remain incompletely understood.

Purpose of the Study:

  • To determine the expression profile of 5HT receptors in murine MIN6 beta cells.
  • To investigate the effects of pharmacological activation of the 5HT receptor Htr2b on GSIS and mitochondrial function.

Main Methods:

  • Quantified 5HT receptor mRNA levels using RT-qPCR.
  • Assessed GSIS in MIN6 cells with 5HT and Htr2b modulation (BW723C86 or SB204741).
  • Evaluated PGC1α and PPARy expression and mitochondrial function (OCR, ATP content) following Htr2b activation.

Main Results:

  • Htr2b mRNA was detected in MIN6 cells, while other 5HT receptors were largely absent.
  • Activation of Htr2b with 5HT or BW723C86 reduced GSIS; this effect was blocked by SB204741.
  • Htr2b activation increased PGC1α and PPARy expression but decreased mitochondrial respiration and ATP levels.

Conclusions:

  • Prolonged Htr2b activation in murine beta cells impairs GSIS and mitochondrial activity.
  • These effects are likely mediated by enhanced PGC1α/PPARy expression.

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