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Diabetologia

Erschienen in:

01.08.2009 | Article

Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

verfasst von: M. Braun, R. Ramracheya, S. Amisten, M. Bengtsson, Y. Moritoh, Q. Zhang, P. R. Johnson, P. Rorsman

Erschienen in: Diabetologia | Ausgabe 8/2009

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Abstract

Aims/hypothesis

The aim of this study was to characterise electrical activity, ion channels, exocytosis and somatostatin release in human delta cells/pancreatic islets.

Methods

Glucose-stimulated somatostatin release was measured from intact human islets. Membrane potential, currents and changes in membrane capacitance (reflecting exocytosis) were recorded from individual human delta cells identified by immunocytochemistry.

Results

Somatostatin secretion from human islets was stimulated by glucose and tolbutamide and inhibited by diazoxide. Human delta cells generated bursting or sporadic electrical activity, which was enhanced by tolbutamide but unaffected by glucose. Delta cells contained a tolbutamide-insensitive, Ba²⁺-sensitive inwardly rectifying K⁺ current and two types of voltage-gated K⁺ currents, sensitive to tetraethylammonium/stromatoxin (delayed rectifying, Kv2.1/2.2) and 4-aminopyridine (A current). Voltage-gated tetrodotoxin (TTX)-sensitive Na⁺ currents contributed to the action potential upstroke but TTX had no effect on somatostatin release. Delta cells are equipped with Ca²⁺ channels blocked by isradipine (L), ω-agatoxin (P/Q) and NNC 55-0396 (T). Blockade of any of these channels interferes with delta cell electrical activity and abolishes glucose-stimulated somatostatin release. Capacitance measurements revealed a slow component of depolarisation-evoked exocytosis sensitive to ω-agatoxin.

Conclusions/interpretation

Action potential firing in delta cells is modulated by ATP-sensitive K⁺-channel activity. The membrane potential is stabilised by Ba²⁺-sensitive inwardly rectifying K⁺ channels. Voltage-gated L- and T-type Ca²⁺ channels are required for electrical activity, whereas Na⁺ currents and P/Q-type Ca²⁺ channels contribute to (but are not necessary for) the upstroke of the action potential. Action potential repolarisation is mediated by A-type and Kv2.1/2.2 K⁺ channels. Exocytosis is tightly linked to Ca²⁺-influx via P/Q-type Ca²⁺ channels. Glucose stimulation of somatostatin secretion involves both K_ATP channel-dependent and -independent processes.

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Titel: Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells
verfasst von: M. Braun
R. Ramracheya
S. Amisten
M. Bengtsson
Y. Moritoh
Q. Zhang
P. R. Johnson
P. Rorsman
Publikationsdatum: 01.08.2009
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 8/2009
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-009-1382-z

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Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

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