SWELL1 is a glucose sensor regulating β-cell excitability and systemic glycaemia.

ABSTRACT: Insulin secretion is initiated by activation of voltage-gated Ca²⁺ channels (VGCC) to trigger Ca²⁺-mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (I_Cl,SWELL) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated I_Cl,SWELL and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling. SWELL1 depletion in MIN6 cells and islets significantly impairs glucose-stimulated insulin secretion. Tamoxifen-inducib

SUBMITTER: Kang C 

PROVIDER: S-EPMC5785485 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature