The diabetes-associated K+ channel TALK-2 controls human beta cell endoplasmic reticulum Ca2+ handling, which promotes basal insulin release and limits glucose-stimulated insulin secretion
These data support the notion that TALK-2 functions on the human beta cell ER membrane to increase the electrical driving force for beta cell Ca<sup>2+</sup><sub>ER</sub> release, reduces glucose-stimulated Ca<sup>2+</sup> influx and limits GSIS. Furthermore, TALK-2-mediated amplification of Ca<sup>2+</sup><sub>ER</sub> leak likely enhances basal insulin secretion by increasing Ca<sup>2+</sup><sub>C</sub>. Therefore, polymorphisms in KCNK17 that increase TALK-2 activity or expression would be predicted to increase type 2 diabetes risk by blunting beta cell glucose-stimulated Ca<sup>2+</sup> influx, limiting GSIS, promoting Ca<sup>2+</sup><sub>ER</sub> leak and elevating basal insulin secretion.
Authors
- MIRIAM CNOP
- Soma Behera
- Spencer J. Peachee (ORCID: https://orcid.org/0009-0004-6147-0046)
- Jordyn R. Dobson
- Prasanna K. Dadi
- David A. Jacobson
- Shannon E. Gibson
- Anthony Piron
- Arya Y. Nakhe
- Matthew T. Dickerson
Institutions
- Université Libre de Bruxelles (BE)
- Vanderbilt University (US)
- Erasmus Hospital (BE)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
Publication Details
- Journal
- Diabetologia
- Published
- 2026-02-25
- DOI
- https://doi.org/10.1007/s00125-026-06683-9
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- European Commission
- Fonds De La Recherche Scientifique - FNRS
- Walloon excellence in life sciences and biotechnology
- National Institutes of Health