Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR.
Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR.
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DOI：
10.1038/ncomms5420
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发表时间：
2014-07-15
影响因子：
16.6
通讯作者：
Chan, Hsiao Chang
中科院分区：
文献类型：
--
作者：
Guo, Jing Hui;Chen, Hui;Ruan, Ye Chun;Zhang, Xue Lian;Zhang, Xiao Hu;Fok, Kin Lam;Tsang, Lai Ling;Yu, Mei Kuen;Huang, Wen Qing;Sun, Xiao;Chung, Yiu Wa;Jiang, Xiaohua;Sohma, Yoshiro;Chan, Hsiao Chang
在许多糖尿病病例中，胰岛素不足的原因仍然未知。高达50%的囊性纤维化（CF）成人患者（一种由编码CF跨膜传导调节因子（CFTR）的基因突变引起的疾病）发展为CF相关糖尿病（CFRD），大多数患者表现出胰岛素不足。在这里，我们表明CFTR是β细胞中葡萄糖依赖性电活动和胰岛素分泌的调节剂。我们证明，在原代小鼠β细胞或RINm 5 F β细胞系中，CFTR抑制剂或敲低可消除或减少葡萄糖引起的全细胞电流、膜去极化、电爆发或动作电位、Ca 2+振荡和胰岛素分泌，或在CFTR突变（DF 508）小鼠中与野生型小鼠相比显著减弱。VX-809是一种新发现的DF 508突变校正剂，成功地挽救了DF 508 β细胞中的缺陷。我们的研究结果揭示了CFTR在葡萄糖诱导的β细胞电活动和胰岛素分泌中的作用，阐明了CFRD和其他可能的特发性糖尿病的发病机制，并提出了一种潜在的治疗策略。 囊性纤维化患者在CFTR氯离子通道中存在突变，并且经常由于尚不清楚的原因而发展为糖尿病。Guo等人在本文中表明，CFTR参与调节葡萄糖刺激的胰腺β细胞胰岛素分泌。
The cause of insulin insufficiency remains unknown in many diabetic cases. Up to 50% adult patients with cystic fibrosis (CF), a disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), develop CF-related diabetes (CFRD) with most patients exhibiting insulin insufficiency. Here we show that CFTR is a regulator of glucose-dependent electrical acitivities and insulin secretion in β-cells. We demonstrate that glucose elicited whole-cell currents, membrane depolarization, electrical bursts or action potentials, Ca2+ oscillations and insulin secretion are abolished or reduced by inhibitors or knockdown of CFTR in primary mouse β-cells or RINm5F β-cell line, or significantly attenuated in CFTR mutant (DF508) mice compared with wild-type mice. VX-809, a newly discovered corrector of DF508 mutation, successfully rescues the defects in DF508 β-cells. Our results reveal a role of CFTR in glucose-induced electrical activities and insulin secretion in β-cells, shed light on the pathogenesis of CFRD and possibly other idiopathic diabetes, and present a potential treatment strategy. Patients with cystic fibrosis harbour mutations in the CFTR chloride channel and often develop diabetes for reasons that are poorly understood. Here Guo et al. show that CFTR is involved in the regulation of glucose-stimulated insulin secretion from pancreatic β-cells.
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影响因子：
56.9
作者：
AMOROSO, S;SCHMIDANTOMARCHI, H;LAZDUNSKI, M
通讯作者：
LAZDUNSKI, M
DOI：
10.1007/978-90-481-3271-3_14
发表时间：
2010-01-01
期刊：
ISLETS OF LANGERHANS
影响因子：
--
作者：
Kasai, Haruo;Hatakeyama, Hiroyasu;Takahashi, Noriko
通讯作者：
Takahashi, Noriko
DOI：
10.1590/s0004-27302011000800016
发表时间：
2011-11-01
期刊：
Arquivos Brasileiros de Endocrinologia & Metabologia
影响因子：
--
作者：
Noronha, Renata Maria de;Calliari, Luís Eduardo Procópio;Monte, Osmar
通讯作者：
Monte, Osmar
影响因子：
3.8
作者：
FISCHER, H;MACHEN, TE
通讯作者：
MACHEN, TE
影响因子：
4.5
作者：
Dahan, D;Evagelidis, A;Zhu, T
通讯作者：
Zhu, T