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Title: Abnormal CFTR affects glucagon production by islet alpha cells in cystic fibrosis and polycystic ovarian syndrome
Authors: Huang, WQ
Guo, JH
Yuan, C
Cui, YG
Diao, FY
Yu, MK 
Liu, JY
Ruan, YC 
Chan, HC
Keywords: CFTR
Islet alpha cell
Cystic fibrosis
Issue Date: 2017
Publisher: Frontiers Research Foundation
Source: Frontiers in physiology, 17 Nov. 2017, v. 8, 835, p. 1-12 How to cite?
Journal: Frontiers in physiology 
Abstract: Glucagon, produced by islet alpha cells, functions to increase blood glucose. Abnormal glucose levels are often seen in cystic fibrosis (CF), a systematic disease caused by mutations of the CF transmembrane conductance regulator (CFTR), and in polycystic ovarian syndrome (PCOS), an endocrine disorder featured with hyperandrogenism affecting 5-10% women of reproductive age. Here, we explored the role of CFTR in glucagon production in alpha cells and its possible contribution to glucagon disturbance in CF and PCOS. We found elevated fasting glucagon levels in CFTR mutant (DF508) mice compared to the wildtypes. Glucagon and prohormone convertase 2 (PC2) were also upregulated in CFTR inhibitor-treated or DF508 islets, as compared to the controls or wildtypes, respectively. Dihydrotestosterone (DHT)-induced PCOS rats exhibited significantly lower fasting glucagon levels with higher CFTR expression in a cells compared to that of controls. Treatment of mouse islets or alpha TC1-9 cells with DHT enhanced CFTR expression and reduced the levels of glucagon and PC2. The inhibitory effect of DHT on glucagon production was blocked by CFTR inhibitors in mouse islets, and mimicked by overexpressing CFTR in alpha TC1-9 cells with reduced phosphorylation of the cAMP/Ca2+ response element binding protein (p-CREB), a key transcription factor for glucagon and PC2. These results revealed a previously undefined role of CFTR in suppressing glucagon production in alpha-cells, defects in which may contribute to glucose metabolic disorder seen in CF and PCOS.
EISSN: 1664-042X
DOI: 10.3389/fphys.2017.00835
Rights: Copyright © 2017 Huang, Guo, Yuan, Cui, Diao, Yu, Liu, Ruan and Chan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) ( The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Huang, W. Q., Guo, J. H., Yuan, C., Cui, Y. G., Diao, F. Y., Yu, M. K., … & Chan, H. C. (2017). Abnormal CFTR affects glucagon production by islet alpha cells in cystic fibrosis and polycystic ovarian syndrome. Frontiers in Physiology, 8, 835, 1-12 is available at
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