Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 β-Cells Treated with Palmitate and Oleate

J Diabetes Res. 2016;2016:3793781. doi: 10.1155/2016/3793781. Epub 2016 Jun 5.

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.

MeSH terms

  • Acetylserotonin O-Methyltransferase / drug effects
  • Acetylserotonin O-Methyltransferase / genetics
  • Animals
  • Arylalkylamine N-Acetyltransferase / drug effects
  • Arylalkylamine N-Acetyltransferase / genetics
  • Catechol O-Methyltransferase / drug effects
  • Catechol O-Methyltransferase / genetics
  • Cell Line
  • Dopa Decarboxylase / drug effects
  • Dopa Decarboxylase / genetics
  • Dopamine Plasma Membrane Transport Proteins / drug effects
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine beta-Hydroxylase / drug effects
  • Dopamine beta-Hydroxylase / genetics
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / metabolism*
  • Mice
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase / genetics
  • Oleic Acid / pharmacology
  • Palmitic Acid / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Transcriptome / drug effects
  • Transcriptome / genetics*
  • Tryptophan Hydroxylase / drug effects
  • Tryptophan Hydroxylase / genetics
  • Tyrosine 3-Monooxygenase / drug effects
  • Tyrosine 3-Monooxygenase / genetics

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Insulin
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a3 protein, mouse
  • Slc6a4 protein, mouse
  • Oleic Acid
  • Palmitic Acid
  • Serotonin
  • Tyrosine 3-Monooxygenase
  • Tph1 protein, mouse
  • Tph2 protein, mouse
  • Tryptophan Hydroxylase
  • Dopamine beta-Hydroxylase
  • Monoamine Oxidase
  • Acetylserotonin O-Methyltransferase
  • COMT protein, mouse
  • Catechol O-Methyltransferase
  • Arylalkylamine N-Acetyltransferase
  • Dopa Decarboxylase