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http://hdl.handle.net/10397/96201
Title: | Glucose-sensitive CFTR suppresses glucagon secretion by potentiating KATP channels in pancreatic islet α cells | Authors: | Huang, WQ Guo, JH Zhang, XH Yu, MK Chung, YW Ruan, YC Chan, HC |
Issue Date: | 1-Oct-2017 | Source: | Endocrinology, 1 Oct. 2017, v. 158, no. 10, p. 3188-3199 | Abstract: | The secretion of glucagon by islet a cells is normally suppressed by high blood glucose, but this suppressibility is impaired in patients with diabetes or cystic fibrosis (CF), a disease caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), a cyclic adenosine monophosphate-activated Cl2 channel. However, precisely how glucose regulates glucagon release remains controversial. Here we report that elevated glucagon secretion, together with increased glucose-induced membrane depolarization and Ca2+ response, is found in CFTR mutant (DF508) mice/islets compared with the wild-Type. Overexpression of CFTR in AlphaTC1-9 cells results in membrane hyperpolarization and reduced glucagon release, which can be reversed by CFTR inhibition. CFTR is found to potentiate the adenosine triphosphate-sensitive K+ (KATP) channel because membrane depolarization and whole-cell currents sensitive to KATP blockers are significantly greater in wild-Type/CFTR-overexpressed a cells compared with that in DF508/nonoverexpressed cells. KATP knockdown also reverses the suppressive effect of CFTR overexpression on glucagon secretion. The results reveal that by potentiating KATP channels, CFTR acts as a glucosesensing negative regulator of glucagon secretion in a cells, a defect of which may contribute to glucose intolerance in CF and other types of diabetes. | Publisher: | Endocrine Society | Journal: | Endocrinology | ISSN: | 0013-7227 | EISSN: | 1945-7170 | DOI: | 10.1210/en.2017-00282 | Rights: | Copyright © 2017 Endocrine Society This is a pre-copyedited, author-produced version of an article accepted for publication in Endocrinology following peer review. The version of record Wen Qing Huang, Jing Hui Guo, Xiao Hu Zhang, Mei Kuen Yu, Yiu Wa Chung, Ye Chun Ruan, Hsiao Chang Chan, Glucose-Sensitive CFTR Suppresses Glucagon Secretion by Potentiating KATP Channels in Pancreatic Islet α Cells, Endocrinology, Volume 158, Issue 10, 1 October 2017, Pages 3188–3199 is available online at: https://doi.org/10.1210/en.2017-00282. |
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Huang_Glucose-sensitive_CFTR_Suppresses.pdf | Pre-Published version | 1.41 MB | Adobe PDF | View/Open |
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