R-type Ca(2+)-channel-evoked CICR regulates glucose-induced somatostatin secretion.
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.
Zhang
Quan
Q
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Bengtsson
Martin
M
Partridge
Chris
C
Salehi
Albert
A
Braun
Matthias
M
Cox
Roger
R
Eliasson
Lena
L
Johnson
Paul R V
PR
Renström
Erik
E
Schneider
Toni
T
Berggren
Per-Olof
PO
Göpel
Sven
S
Ashcroft
Frances M
FM
Rorsman
Patrik
P
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
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