BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases ß cell mass.
Cell Metab
; 34(11): 1779-1791.e9, 2022 11 01.
Article
en En
| MEDLINE
| ID: mdl-36240759
ABSTRACT
Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. We report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing ß cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets. We detail BefA's atomic structure, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand ß cells, whereas the pore-forming host defense protein, Reg3, stimulates ß cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defense proteins is necessary and sufficient for ß cell expansion during pancreas development, potentially connecting microbiome composition with diabetes risk.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus
/
Microbiota
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos