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

Figure 6

Outline of serotoninergic and dopaminergic systems in β-cells and its role in insulin secretion. Glucose enters into pancreatic β-cell via the insulin independent glucose transporter (Glut2 in mice), allowing its metabolism through glycolysis, Krebs cycle, and oxidative phosphorylation. The increase in the ATP/ADP ratio induces the inhibition of the ATP dependent potassium channel and consequently the plasma membrane depolarization, triggering the extracellular calcium uptake and the insulin granules exocytosis. Both serotonin precursors, 5HTP and L-tryptophan, and the dopamine precursors, L-tyrosine and L-Dopa, can enter into the β-cell by the LAAT transporter. The first two precursors may be converted to serotonin by action of the enzymes TPH1/2 and DDC, while the latter precursors could be converted to dopamine by the enzymes TH and DDC. These newly synthesized monoamines are stored in the secretory granules by the vesicular carriers (VMAT1/2). In response to glucose stimuli, the β-cells can release insulin, together with serotonin and dopamine. Therefore, both extracellular monoamines can exert their actions on insulin secretion depending on which specific receptors are activated. Serotonin and dopamine may inhibit the glucose-stimulated insulin secretion acting by Htr2c and D3 receptors, respectively. We propose that the exposure of pancreatic β-cells to the nonesterified fatty acids, palmitic and oleic acids, may lead to a decreased expression of Maob and thus an accumulation of the monoamines, serotonin and dopamine. When these monoamines are released, they signal through their specific receptors, which may contribute to a decreased glucose-stimulated insulin secretion.