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

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number4420
JournalNature communications
Volume5
DOIs
Publication statusPublished - 2014 Jul 15

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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