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Relative contribution of Ca 2+ ‐dependent and Ca 2+ ‐independent mechanisms to the regulation of insulin secretion by glucose
Author(s) -
Sato Yoshihiko,
Nenquin Myriam,
Henquin Jean-Claude
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01547-0
Subject(s) - forskolin , medicine , exocytosis , endocrinology , insulin , glucagon , diazoxide , chemistry , calcium , islet , secretion , calmodulin , acetylcholine , biophysics , biology , stimulation
Although insulin secretion is usually regarded as a Ca 2+ ‐dependent mechanism, recent studies have suggested the existence of a Ca 2+ ‐independent pathway of regulation by glucose. Here, mouse islets were used to compare the contribution of Ca 2+ ‐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 [Ca 2+ ] i (triggering signal), and in the presence of 30 mM K + and diazoxide, when it does not further raise [Ca 2+ ] i but increases its efficacy on exocytosis. Both Ca 2+ ‐dependent responses were amplified by glucagon‐like peptide‐1+acetylcholine, and were strongly potentiated by forskolin+PMA. Under conditions of mild or stringent Ca 2+ 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 Ca 2+ ‐dependent pathways without significant contribution of a Ca 2+ ‐independent mechanism.