Glucose-induced electrical activities and insulin secretion in pancreatic islet 2-cells are modulated by CFTR

Jing Hui Guo, Hui Chen, Ye Chun Ruan, Xue Lian Zhang, Xiao Hu Zhang, Kin Lam Fok, Lai Ling Tsang, Mei Kuen Yu, Wen Qing Huang, Xiao Sun, Yiu Wa Chung, Xiaohua Jiang, Yoshiro Sohma, Hsiao Chang Chan

研究成果: Article査読

101 被引用数 (Scopus)

抄録

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 2-cells. We demonstrate that glucose elicited whole-cell currents, membrane depolarization, electrical bursts or action potentials, Ca 2+ oscillations and insulin secretion are abolished or reduced by inhibitors or knockdown of CFTR in primary mouse 2-cells or RINm5F 2-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 2-cells. Our results reveal a role of CFTR in glucose-induced electrical activities and insulin secretion in 2-cells, shed light on the pathogenesis of CFRD and possibly other idiopathic diabetes, and present a potential treatment strategy.

本文言語English
論文番号4420
ジャーナルNature communications
5
DOI
出版ステータスPublished - 2014 7 15
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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