Relative contribution of Ca2+‐dependent and Ca2+‐independent mechanisms to the regulation of insulin secretion by glucose

FEBS Letters

Henquin, Jean-Claude¹  Nenquin, Myriam¹  Sato, Yoshihiko¹ 

[1] Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium

关键词: Insulin release;    Stimulus-secretion coupling;    Calcium;    Glucose;    Protein kinase;    Pancreatic islet;   

DOI  :  10.1016/S0014-5793(97)01547-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Although insulin secretion is usually regarded as a Ca²⁺-dependent mechanism, recent studies have suggested the existence of a Ca²⁺-independent pathway of regulation by glucose. Here, mouse islets were used to compare the contribution of Ca²⁺-dependent and -independent pathways. Glucose increased insulin release in a concentration-dependent manner both in a control medium, when it depolarizes β cells and raises [Ca²⁺]_i (triggering signal), and in the presence of 30 mM K⁺ and diazoxide, when it does not further raise [Ca²⁺]_i but increases its efficacy on exocytosis. Both Ca²⁺-dependent responses were amplified by glucagon-like peptide-1+acetylcholine, and were strongly potentiated by forskolin+PMA. Under conditions of mild or stringent Ca²⁺ deprivation, glucose had no effect either alone or with GLP-1 and acetylcholine, and was poorly effective even during pharmacological activation of protein kinases A and C. Similar results were obtained with rat islets. It is concluded that physiological regulation of insulin release by glucose is essentially achieved through the two Ca²⁺-dependent pathways without significant contribution of a Ca²⁺-independent mechanism.

【 授权许可】

Unknown