Letter abstract
Nature Cell Biology 9, 453 - 460 (2007)
Published online: 18 March 2007 | doi:10.1038/ncb1563
R-type Ca2+-channel-evoked CICR regulates glucose-induced somatostatin secretion
Quan Zhang1,2, Martin Bengtsson2, Chris Partridge1, Albert Salehi2, Matthias Braun1, Roger Cox3, Lena Eliasson2, Paul RV Johnson4, Erik Renström2, Toni Schneider5, Per-Olof Berggren6, Sven Göpel7, Frances M Ashcroft8 & Patrik Rorsman1
Pancreatic islets have a central role in blood glucose homeostasis. In addition to insulin-producing 
-cells and glucagon-secreting 
-cells, the islets contain somatostatin-releasing 
-cells1. Somatostatin is a powerful inhibitor of insulin and glucagon secretion2. It is normally secreted in response to glucose3 and there is evidence suggesting its release becomes perturbed in diabetes4. Little is known about the control of somatostatin release. Closure of ATP-regulated K+-channels (KATP-channels)5 and a depolarization-evoked increase in cytoplasmic free Ca2+ concentration ([Ca2+]i)6, 7, 8 have been proposed to be essential. Here, we report that somatostatin release evoked by high glucose (
10 mM) is unaffected by the KATP-channel activator diazoxide and proceeds normally in KATP-channel-deficient islets. Glucose-induced somatostatin secretion is instead primarily dependent on Ca2+-induced Ca2+-release (CICR). This constitutes a novel mechanism for KATP-channel-independent metabolic control of pancreatic hormone secretion.
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
- Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden.
- MRC Mammalian Genetics Unit, Medical Research Council, Harwell, Didcot OX11 0RD, UK.
- Nuffield Department of Surgery, Level 6, John Radcliffe Hospital, Oxford OX3 9DU, UK.
- Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, D-50931 Köln, Germany.
- The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet SE-171 76 Stockholm, Sweden.
- AstraZeneca R&D, Pepparedsleden 1, SE-43183 Mölndal, Sweden.
- Department of Physiology, Anatomy and Genetics, Parks Road, University of Oxford, Oxford OX1 3PT, UK.
Correspondence to: Patrik Rorsman1 e-mail: patrik.rorsman@drl.ox.ac.uk
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