Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Norepinephrine Inhibits Glucose-Stimulated, Ca2+-Independent Insulin Release Independently from Its Action on Adenylyl Cyclase
HIROKI YAJIMAMITSUHISA KOMATSUYOSHIHIKO SATOSATOKO YAMADAKEISHI YAMAUCHIGEOFFREY W. G. SHARPTORU AIZAWAKIYOSHI HASHIZUME
Author information
JOURNAL FREE ACCESS

2001 Volume 48 Issue 6 Pages 647-654

Details
Abstract

Inhibition of insulin release by norepinephrine has been attributed to activation of ATP-sensitive K+ channels, inactivation of voltage-dependent Ca2+ 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-permeabilized β cells. In rat pancreatic islets, a combination of glucose, phorbol ester and forskolin under stringent Ca2+-free conditions was used as a trigger of insulin exocytosis at a distal site. Norepinephrine inhibited this Ca2+-independent insulin release in a concentration-dependent manner, with an IC50 of 50nM. The inhibition was complete, reversible, and pertussis toxin-sensitive, and not associated with any reduction of cAMP content in the islet cells. In conclusion, norepinephrine strongly, yet reversibly, inhibits insulin release in intact β cells at a late step of exocytosis, through pertussis toxin-sensitive, G protein-mediated mechanism(s).

Content from these authors
© The Japan Endocrine Society
Previous article Next article
feedback
Top