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. Author manuscript; available in PMC: 2013 Oct 1.
Published in final edited form as: Diabetes Obes Metab. 2012 Oct;14(0 3):91–100. doi: 10.1111/j.1463-1326.2012.01651.x

Figure 1.

Figure 1

Schematic of a putative dopamine mediated autocrine negative feedback circuit in β-cells. Import of aromatic amino acids (Tyrosine [Try] and Tryptophan [Trp]) by neutral amino acid carriers (LAT1) from extracellular space occurs, followed by transformation of Typ and Trp to L-DOPA and 5-hydroxy-tryptophan (5-OH-TRP) by the action of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH). Both L-DOPA and 5-OH-TRP are transformed into dopamine (DA) and serotonin (5-HT) by the action of aromatic amino acid decarboxylase (AADC).Cytoplasmic DA or 5-HT are transported by VMAT2 into β-cell vesicles and later delivered to the intracellular space following glucose stimulated insulin secretion. Dopamine type 2 receptors are stored in vesicles, rendered inactive in the acid microenvironment. Extracellular dopamine (e.g. as elevated dopamine sulfate found in postprandial serum samples can shuttled inside the β-cell by the action of the dopamine transporter (DAT). DA and 5-HT not sequestered by the action of VMAT2 is exposed to the action of monoamine oxidase and destructively metabolized.