Norepinephrine inhibits glucose-stimulated, Ca~2+ -independ- ent insulin release independently from its action on adenylyl cyclase

摘要

Inhibition of insulin release by norepinephrine has been attributed to activation of ATP-sensitive K~+ channels, inactivation of voltage-dependent Ca~2+ channels, and inhibition of adenylyl cyclase. However, direct inhibitory action of norepinephrine at a distal site of stimulus-secretion coupling has also been suggested. To obtain more direct evidence for norepinephrine inhibition of insulin release at a distal site, we performed experiments in intact, non-permeabilizedβcells. In rat pancreatic islets, a combination of glucose, phorbal ester and forskolin under stringent Ca~2+ -free conditions was used as a trigger of insulin exocytosis at a distal site.