title: Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 β-Cells Treated with Palmitate and Oleate.
abstract: High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent β-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated β-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 β-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 β-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (-25%; p < 0.0001) and oleate (-43%; p < 0.0001) were detected in MIN6 β-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 β-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile; Facultad de Medicina, Universidad de los Andes, 7620001 Santiago, Chile.
authors.forename: L R
authors.initials: LR
authors.lastname: Cataldo
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: M L
authors.identifier: 0000-0002-6396-8823
authors.initials: ML
authors.lastname: Mizgier
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: D
authors.identifier: 0000-0003-2113-1926
authors.initials: D
authors.lastname: Busso
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Olmos
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile; UDA-Ciencias de la Salud, Carrera de Nutrición y Dietética, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: J E
authors.initials: JE
authors.lastname: Galgani
authors.affiliation: Departamento de Nutrición, Facultad de Medicina, Universidad de Chile, 7550367 Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Valenzuela
authors.affiliation: Laboratorio de Hemostasia, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: D
authors.identifier: 0000-0003-2448-9288
authors.initials: D
authors.lastname: Mezzano
authors.affiliation: Laboratorio de Hemostasia, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: E
authors.initials: E
authors.lastname: Aranda
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: V A
authors.initials: VA
authors.lastname: Cortés
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: J L
authors.initials: JL
authors.lastname: Santos
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000187:drug effects / Q000235:genetics; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000187:drug effects / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D004296:Dopa Decarboxylase / Q000187:drug effects / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000187:drug effects / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008995:Monoamine Oxidase / Q000187:drug effects / Q000235:genetics; D019301:Oleic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000187:drug effects / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000235:genetics
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007328:Insulin; D050486:Serotonin Plasma Membrane Transport Proteins; C493215:Slc6a3 protein, mouse; C493231:Slc6a4 protein, mouse; D019301:Oleic Acid; D019308:Palmitic Acid; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; C487801:Tph1 protein, mouse; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase; D004299:Dopamine beta-Hydroxylase; D008995:Monoamine Oxidase; D000121:Acetylserotonin O-Methyltransferase; C000593198:COMT protein, mouse; D002394:Catechol O-Methyltransferase; D047068:Arylalkylamine N-Acetyltransferase; D004296:Dopa Decarboxylase