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

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Sato, Y Nenquin, Myriam [UCL] Henquin, Jean-Claude [UCL]

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 beta 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.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 1998
Journal information "FEBS letters" - Vol. 421, no. 2, p. 115-9 (1998)
Peer reviewed yes
issn 0014-5793
Publication status Publié
Affiliation UCL - MD/FSIO - Département de physiologie et pharmacologie
MESH Subject Animals ; Calcium - metabolism - pharmacology ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Female ; Glucose - metabolism - pharmacology ; Insulin - secretion ; Islets of Langerhans - drug effects - metabolism ; Mice ; Protein Kinase C - metabolism ; Rats ; Rats, Wistar
Links
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Bibliographic reference Sato, Y ; Nenquin, Myriam ; Henquin, Jean-Claude. Relative contribution of Ca2+-dependent and Ca2+-independent mechanisms to the regulation of insulin secretion by glucose.. In: FEBS letters, Vol. 421, no. 2, p. 115-9 (1998)
Permanent URL http://hdl.handle.net/2078.1/13129