Fig. 1: Human and mouse pancreatic α- and β-cells express the catecholaminergic machinery with α-cell production of catecholamines and metabolites.

a, b Transcriptome by RNA-sequencing analysis of purified α- and β-cells from pancreatic islets from a non-diabetic human donors (n = 5; ages 26–55 years) and b mouse. Heatmaps of a selected gene subset focusing on the catecholamine biosynthetic, transport, and vesicular packaging machinery show relative gene expression values in individual α- and β-cell samples of dopaminergic and adrenergic receptors as well as the complete catecholamine biosynthetic and catabolic machinery. c HPLC analyses of supernatants and lysates from α-cell-derived αTC1–6 cells demonstrating the synthesis of L-DOPA, DA, and NE de novo in the absence of catecholamine precursor supplementation. Cells secreted most intracellular L-DOPA and DA with significantly lower L-DOPA (P = 0.0002) or DA (P < 0.05) in lysates compared to supernatants. d HPLC analyses show that pre-incubation with 10 μM L-DOPA significantly enhanced α-cell DA and NE production and secretion. Though L-DOPA supplementation boosted NE production (P = 0.0004), DA production was preferentially boosted over NE, with DA levels 27-fold more compared to NE (P < 0.0001). e, f In αTC1–6 cells, both secreted and intracellular levels of DA metabolites HVA (e) and DOPAC (f) were substantially enhanced in response to 10 μM L-DOPA supplementation. g Treatment of αTC1–6 cells with a cocktail of monoamine oxidase inhibitors (MAOIs: 10 μM of deprenyl, pargyline, and clorgyline, respectively) significantly enhanced DA synthesis in response to L-DOPA supplementation (blue bar) compared to the 10 μM L-DOPA alone condition (P < 0.0001, gray bar). Assay points were carried out in triplicates from n ≥ 2 independent experiments. Data are represented as mean ± SEM; two-tailed Student’s t-test (c, d, g). *P < 0.05, ***P < 0.001, ****P < 0.0001.