title: R-type Ca(2+)-channel-evoked CICR regulates glucose-induced somatostatin secretion.
abstract: Pancreatic islets have a central role in blood glucose homeostasis. In addition to insulin-producing beta-cells and glucagon-secreting alpha-cells, the islets contain somatostatin-releasing delta-cells. Somatostatin is a powerful inhibitor of insulin and glucagon secretion. It is normally secreted in response to glucose and there is evidence suggesting its release becomes perturbed in diabetes. Little is known about the control of somatostatin release. Closure of ATP-regulated K(+)-channels (K(ATP)-channels) and a depolarization-evoked increase in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) have been proposed to be essential. Here, we report that somatostatin release evoked by high glucose (>or=10 mM) is unaffected by the K(ATP)-channel activator diazoxide and proceeds normally in K(ATP)-channel-deficient islets. Glucose-induced somatostatin secretion is instead primarily dependent on Ca(2+)-induced Ca(2+)-release (CICR). This constitutes a novel mechanism for K(ATP)-channel-independent metabolic control of pancreatic hormone secretion.
authors: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
authors: Quan
authors: Q
authors: Zhang
authors: Martin
authors: M
authors: Bengtsson
authors: Chris
authors: C
authors: Partridge
authors: Albert
authors: A
authors: Salehi
authors: Matthias
authors: M
authors: Braun
authors: Roger
authors: R
authors: Cox
authors: Lena
authors: L
authors: Eliasson
authors: Paul R V
authors: PR
authors: Johnson
authors: Erik
authors: E
authors: Renström
authors: Toni
authors: T
authors: Schneider
authors: Per-Olof
authors: PO
authors: Berggren
authors: Sven
authors: S
authors: Göpel
authors: Frances M
authors: FM
authors: Ashcroft
authors: Patrik
authors: P
authors: Rorsman
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020908:Calcium Channels, R-Type / Q000235:genetics / Q000502:physiology*; D003592:Cytophotometry; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017275:Isradipine / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008356:Mannoheptulose / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010080:Oxazoles / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism*; D019864:Somatostatin-Secreting Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D020908:Calcium Channels, R-Type; D047028:Macrocyclic Compounds; D010080:Oxazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C511704:xestospongin C; D012433:Ryanodine; D013004:Somatostatin; D008356:Mannoheptulose; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D002118:Calcium; D017275:Isradipine