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. beta-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated. beta-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 beta-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 beta-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 beta-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 beta-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content