A role for vagal activity in preventing the suppression of glucagon secretion by GLP-1 during hypoglycemia

Autonomic signaling suppresses somatostatin secretion, crucial for paracrine stimulation of glucagon secretion. SST mediates GLP-1-induced inhibition of glucagon secretion, but autonomic signaling may interfere with this mechanism. Activation of cholinergic pathways in a preparation with prepancreatic parasympathetic structures suppresses SST secretion in response to GLP-1 and potentiates glucagon secretion during hypoglycemia. These findings support the clinical importance of autonomic signaling in regulating pancreatic hormone secretion and hypoglycemia risk in some patients on GLP-1 receptor agonists.