Bri2 BRICHOS domain inhibits IAPP amyloid formation and improves beta cell function in stem cell-derived islets under metabolic stress
Our findings suggest that the molecular chaperone Bri2 colocalises with IAPP and insulin in SC-islet beta cells. The folding assistance has been ascribed to the BRICHOS domain in Bri2 and viral overexpression of the BRICHOS domain can prevent the formation of cytotoxic IAPP amyloid and improve beta cell function in SC-islets exposed to metabolic stress. A comprehensive analysis of SC-islet functionality excludes beta cell impairment as a cause for amyloid reduction but supports the protection against IAPP amyloid.
Authors
- Robin S. Lindsay (ORCID: https://orcid.org/0000-0001-7867-8653)
- Jing Cen (ORCID: https://orcid.org/0000-0001-6014-3984)
- Svitlana Vasylovska (ORCID: https://orcid.org/0000-0003-0682-3449)
- Joey Lau (ORCID: https://orcid.org/0000-0002-8302-3253)
- Gunilla T. Westermark (ORCID: https://orcid.org/0000-0003-1151-9986)
- Anja Ivis (ORCID: https://orcid.org/0000-0001-5991-7137)
- Kina Adjieva (ORCID: https://orcid.org/0009-0005-3729-3593)
Institutions
- Uppsala University (SE)
Publication Details
- Journal
- Diabetologia
- Published
- 2025-11-10
- DOI
- https://doi.org/10.1007/s00125-025-06582-5
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Novo Nordisk
- Uppsala Universitet
- Novo Nordisk Fonden