Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events

Agonists for glucagon-like-peptide-1 receptor (GLP-1R) are currently used for the treatment of type 2 diabetes and obesity. Their benefits have been centered on pancreas and hypothalamus, but their roles in other organ systems are not well understood. We studied the action of GLP-1R on secretions of adrenal medulla. Exendin-4, a synthetic analog of GLP-1, increases the synthesis and the release of catecholamines (CAs) by increasing cyclic AMP (cAMP) production, without apparent participation of cAMP-regulated guanine nucleotide exchange factor (Epac). Exendin-4, when incubated for 24 h, increases CA synthesis by promoting the activation of tyrosine hydroxylase. Short incubation (20 min) increases the quantum size of exocytotic events by switching exocytosis from partial to full fusion. Our results give a strong support to the role of GLP-1 in the fine control of exocytosis.

Automated summary

Glucagon-like-peptide-1 receptor agonists are commonly used for treating type 2 diabetes and obesity, with benefits focused on the pancreas and hypothalamus. However, the role of GLP-1R in adrenal medulla secretions is less understood. Experiments show that Exendin-4 enhances catecholamine synthesis and release through cAMP production, while also regulating the quantum size of exocytotic events.