Block of Kv1.7 potassium currents increases glucose‐stimulated insulin secretion

Glucose‐stimulated insulin secretion (GSIS) relies on repetitive, electrical spiking activity of the beta cell membrane. Cyclic activation of voltage‐gated potassium channels (K v ) generates an outward, ‘delayed rectifier’ potassium current, which drives the repolarizing phase of each spike and mod...

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Bibliographic Details
Published in:EMBO molecular medicine 2012-05, Vol.4 (5), p.424-434
Main Authors: Finol‐Urdaneta, Rocio K., Remedi, Maria S., Raasch, Walter, Becker, Stefan, Clark, Robert B., Strüver, Nina, Pavlov, Evgeny, Nichols, Colin G., French, Robert J., Terlau, Heinrich
Format: Article
Language:English
Subjects:
Animals
Bodily Secretions
Conkunitzin‐S1
electrical signalling
Glucose - metabolism
GSIS
Humans
Insulin - metabolism
Insulin Secretion
Male
Mollusk Venoms - toxicity
pancreas
Potassium - metabolism
potassium channels
Rats
Rats, Wistar
Research Article
Shaker Superfamily of Potassium Channels - antagonists & inhibitors
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Summary:Glucose‐stimulated insulin secretion (GSIS) relies on repetitive, electrical spiking activity of the beta cell membrane. Cyclic activation of voltage‐gated potassium channels (K v ) generates an outward, ‘delayed rectifier’ potassium current, which drives the repolarizing phase of each spike and modulates insulin release. Although several K v channels are expressed in pancreatic islets, their individual contributions to GSIS remain incompletely understood. We take advantage of a naturally occurring cone‐snail peptide toxin, Conkunitzin‐S1 (Conk‐S1), which selectively blocks K v 1.7 channels to provide an intrinsically limited, finely graded control of total beta cell delayed rectifier current and hence of GSIS. Conk‐S1 increases GSIS in isolated rat islets, likely by reducing K v 1.7‐mediated delayed rectifier currents in beta cells, which yields increases in action potential firing and cytoplasmic free calcium. In rats, Conk‐S1 increases glucose‐dependent insulin secretion without decreasing basal glucose. Thus, we conclude that K v 1.7 contributes to the membrane‐repolarizing current of beta cells during GSIS and that block of this specific component of beta cell K v current offers a potential strategy for enhancing GSIS with minimal risk of hypoglycaemia during metabolic disorders such as Type 2 diabetes.
ISSN:1757-4676
1757-4684
DOI:10.1002/emmm.201200218