CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells

Abstract Glucagon is the main counterregulatory hormone in the body. Still, the mechanism involved in the regulation of glucagon secretion from pancreatic alpha cells remains elusive. Dysregulated glucagon secretion is common in patients with Cystic Fibrosis (CF) that develop CF related diabetes (CF...

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Autores principales:	Anna Edlund, Morten Gram Pedersen, Andreas Lindqvist, Nils Wierup, Malin Flodström-Tullberg, Lena Eliasson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4e5082688ab0421091e36c36b8736363
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spelling	oai:doaj.org-article:4e5082688ab0421091e36c36b87363632021-12-02T12:31:47ZCFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells10.1038/s41598-017-00098-82045-2322https://doaj.org/article/4e5082688ab0421091e36c36b87363632017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00098-8https://doaj.org/toc/2045-2322Abstract Glucagon is the main counterregulatory hormone in the body. Still, the mechanism involved in the regulation of glucagon secretion from pancreatic alpha cells remains elusive. Dysregulated glucagon secretion is common in patients with Cystic Fibrosis (CF) that develop CF related diabetes (CFRD). CF is caused by a mutation in the Cl− channel Cystic fibrosis transmembrane conductance regulator (CFTR), but whether CFTR is present in human alpha cells and regulate glucagon secretion has not been investigated in detail. Here, both human and mouse alpha cells showed CFTR protein expression, whereas CFTR was absent in somatostatin secreting delta cells. CFTR-current activity induced by cAMP was measured in single alpha cells. Glucagon secretion at different glucose levels and in the presence of forskolin was increased by CFTR-inhibition in human islets, whereas depolarization-induced glucagon secretion was unaffected. CFTR is suggested to mainly regulate the membrane potential through an intrinsic alpha cell effect, as supported by a mathematical model of alpha cell electrophysiology. In conclusion, CFTR channels are present in alpha cells and act as important negative regulators of cAMP-enhanced glucagon secretion through effects on alpha cell membrane potential. Our data support that loss-of-function mutations in CFTR contributes to dysregulated glucagon secretion in CFRD.Anna EdlundMorten Gram PedersenAndreas LindqvistNils WierupMalin Flodström-TullbergLena EliassonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Edlund Morten Gram Pedersen Andreas Lindqvist Nils Wierup Malin Flodström-Tullberg Lena Eliasson CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
description	Abstract Glucagon is the main counterregulatory hormone in the body. Still, the mechanism involved in the regulation of glucagon secretion from pancreatic alpha cells remains elusive. Dysregulated glucagon secretion is common in patients with Cystic Fibrosis (CF) that develop CF related diabetes (CFRD). CF is caused by a mutation in the Cl− channel Cystic fibrosis transmembrane conductance regulator (CFTR), but whether CFTR is present in human alpha cells and regulate glucagon secretion has not been investigated in detail. Here, both human and mouse alpha cells showed CFTR protein expression, whereas CFTR was absent in somatostatin secreting delta cells. CFTR-current activity induced by cAMP was measured in single alpha cells. Glucagon secretion at different glucose levels and in the presence of forskolin was increased by CFTR-inhibition in human islets, whereas depolarization-induced glucagon secretion was unaffected. CFTR is suggested to mainly regulate the membrane potential through an intrinsic alpha cell effect, as supported by a mathematical model of alpha cell electrophysiology. In conclusion, CFTR channels are present in alpha cells and act as important negative regulators of cAMP-enhanced glucagon secretion through effects on alpha cell membrane potential. Our data support that loss-of-function mutations in CFTR contributes to dysregulated glucagon secretion in CFRD.
format	article
author	Anna Edlund Morten Gram Pedersen Andreas Lindqvist Nils Wierup Malin Flodström-Tullberg Lena Eliasson
author_facet	Anna Edlund Morten Gram Pedersen Andreas Lindqvist Nils Wierup Malin Flodström-Tullberg Lena Eliasson
author_sort	Anna Edlund
title	CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
title_short	CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
title_full	CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
title_fullStr	CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
title_full_unstemmed	CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
title_sort	cftr is involved in the regulation of glucagon secretion in human and rodent alpha cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4e5082688ab0421091e36c36b8736363
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CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells

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