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

Abstract EN

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.