title: Prolonged Activation of the Htr2b Serotonin Receptor Impairs Glucose Stimulated Insulin Secretion and Mitochondrial Function in MIN6 Cells.
abstract: OBJECTIVE
  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.
  
  
  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 glucose-stimulated insulin secretion and mitochondrial activity by mechanisms likely dependent on enhanced PGC1α/PPARy expression.
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Luis Rodrigo
authors.initials: LR
authors.lastname: Cataldo
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: María L
authors.initials: ML
authors.lastname: Mizgier
authors.affiliation: Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bravo Sagua
authors.affiliation: Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
authors.forename: Fabián
authors.initials: F
authors.lastname: Jaña
authors.affiliation: Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.|Geroscience Center for Brain Health and Metabolism, Santiago, Chile.|Buck Institute for Research on Aging, Novato, CA, United States of America.
authors.forename: César
authors.initials: C
authors.lastname: Cárdenas
authors.affiliation: Institute for Research in Dental Sciences, School of Odontology, University of Chile, Santiago, Chile.
authors.forename: Paola
authors.initials: P
authors.lastname: Llanos
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Dolores
authors.initials: D
authors.lastname: Busso
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Olmos
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|UDA-Health Sciences, Nutrition and Dietetic Program, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: José E
authors.initials: JE
authors.lastname: Galgani
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: José L
authors.initials: JL
authors.lastname: Santos
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Víctor A
authors.initials: VA
authors.lastname: Cortés
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000096:biosynthesis / Q000235:genetics*; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000235:genetics*; D012701:Serotonin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D007211:Indoles; D007328:Insulin; C092756:N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011985:Receptors, Serotonin; D013876:Thiophenes; D012701:Serotonin; D000255:Adenosine Triphosphate; D014508:Urea; D005947:Glucose