| First Author | Kang C | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 367 |
| PubMed ID | 29371604 | Mgi Jnum | J:258611 |
| Mgi Id | MGI:6114815 | Doi | 10.1038/s41467-017-02664-0 |
| Citation | Kang C, et al. (2018) SWELL1 is a glucose sensor regulating beta-cell excitability and systemic glycaemia. Nat Commun 9(1):367 |
| abstractText | Insulin secretion is initiated by activation of voltage-gated Ca(2+) channels (VGCC) to trigger Ca(2+)-mediated insulin vesicle fusion with the beta-cell plasma membrane. The firing of VGCC requires beta-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 (ICl,SWELL) in both murine and human beta-cells. Hypotonic and glucose-stimulated beta-cell swelling activates SWELL1-mediated ICl,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-inducible beta-cell-targeted Swell1 KO mice have normal fasting serum glucose and insulin levels but impaired glucose-stimulated insulin secretion and glucose tolerance; and this is further exacerbated in mild obesity. Our results reveal that beta-cell SWELL1 modulates insulin secretion and systemic glycaemia by linking glucose-mediated beta-cell swelling to membrane depolarization and activation of VGCC-triggered calcium signaling. |
