We and colleagues showed that D2R/D3R can regulate both insulin and dopamine release directly in pancreatic beta cells from humans and rodents independently of CNS control.17–20 Specifically, we found that pancreatic dopamine inhibits glucose-stimulated insulin secretion (GSIS) via beta cell D2R/D3R, through an autocrine/paracrine mechanism.18, 20 Conversely, APD blockade of D2R/D3R significantly enhances GSIS.18 Importantly, this APD-induced increase in insulin secretion reproduces aspects of the chronic hyperinsulinemia found in T2D21 (Fig. 1). The gene discussed is INS; the disease is hyperinsulinism.