Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic β-cells.

ABSTRACT: KCNQ1/Kv7, a low-voltage-gated K⁺ channel, regulates cardiac rhythm and glucose homeostasis. While KCNQ1 mutations are associated with long-QT syndrome and type2 diabetes, its function in human pancreatic cells remains controversial. We identified a homozygous KCNQ1 mutation (R397W) in an individual with permanent neonatal diabetes melitus (PNDM) without cardiovascular symptoms. To decipher the potential mechanism(s), we introduced the mutation into human embryonic stem cells and generated islet-like organoids (SC-islets) using CRISPR-mediated homology-repair. The mutation did not affect pancreatic differentiation, but affected channel function by increasing spike frequency and Ca²⁺ flux, leading to insulin hypersecretion. With prolonged culturing, the m

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC11269803 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature