Norepinephrine Inhibits Glucose-Stimulated, Ca2+-Independent Insulin Release Independently from Its Action on Adenylyl Cyclase

Endocrine Journal

YOSHIHIKO SATO¹  KEISHI YAMAUCHI¹  HIROKI YAJIMA¹  KIYOSHI HASHIZUME¹  GEOFFREY W. G. SHARP²  MITSUHISA KOMATSU¹  SATOKO YAMADA¹  TORU AIZAWA¹ 

[1] Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine;Department of Molecular Medicine, College of Veterinary Medicine, Cornell University

关键词: Insulin secretion;    Norepinephrine;    Calcium;    Pertussis toxin;   

DOI  :  10.1507/endocrj.48.647

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(29)Cited-By(6)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).

【 授权许可】

Unknown