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• W1603933329 abstract "Post-translational modification by the small ubiquitin-like modifier-1 (SUMO1) limits insulin secretion from β-cells by inhibiting insulin exocytosis and glucagon-like peptide-1 (GLP-1) receptor signalling. The secretion of glucagon from α-cells is regulated in a manner opposite to that of insulin; it is inhibited by elevated glucose and GLP-1, and increased by adrenergic signalling. We therefore sought to determine whether SUMO1 modulates mouse and human α-cell function. Action potentials (APs), ion channel function and exocytosis in single α-cells from mice and humans, identified by glucagon immunostaining, and glucagon secretion from intact islets were measured. The effects of SUMO1 on α-cell function and the respective inhibitory and stimulatory effects of exendin 4 and adrenaline were examined. Upregulation of SUMO1 increased α-cell AP duration, frequency and amplitude, in part as a result of increased Ca(2+) channel activity that led to elevated exocytosis. The ability of SUMO1 to enhance α-cell exocytosis was cAMP-dependent and resulted from an increased L-type Ca(2+) current and a shift away from exocytosis dependent on non-L-type channels, an effect that was mimicked by knockdown of the deSUMOylating enzyme sentrin/SUMO-specific protease-1 (SENP1). Finally, although SUMO1 prevented GLP-1 receptor-mediated inhibition of α-cell Na(+) channels and single-cell exocytosis, it failed to prevent the exendin 4-mediated inhibition of glucagon secretion. Consistent with its cAMP dependence, however, SUMO1 enhanced α-cell exocytosis and glucagon secretion stimulated by adrenaline. Thus, by contrast with its inhibitory role in β-cell exocytosis, SUMO1 is a positive regulator of α-cell exocytosis and glucagon secretion under conditions of elevated cAMP." @default.
• W1603933329 created "2016-06-24" @default.
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• W1603933329 date "2014-07-11" @default.
• W1603933329 modified "2023-10-12" @default.
• W1603933329 title "SUMO1 enhances cAMP-dependent exocytosis and glucagon secretion from pancreatic α-cells" @default.
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• W1603933329 doi "https://doi.org/10.1113/jphysiol.2014.274084" @default.
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