Type 2 diabetes susceptibility gene GRK5 regulates physiological pancreatic ß-cell proliferation via phosphorylation of HDAC5.
iScience
; 26(8): 107311, 2023 Aug 18.
Article
en En
| MEDLINE
| ID: mdl-37520700
ABSTRACT
Restoring functional ß cell mass is a potential therapy for those with diabetes. However, the pathways regulating ß cell mass are not fully understood. Previously, we demonstrated that Sox4 is required for ß cell proliferation during prediabetes. Here, we report that Sox4 regulates ß cell mass through modulating expression of the type 2 diabetes (T2D) susceptibility gene GRK5. ß cell-specific Grk5 knockout mice showed impaired glucose tolerance with reduced ß cell mass, which was accompanied by upregulation of cell cycle inhibitor gene Cdkn1a. Furthermore, we found that Grk5 may drive ß cell proliferation through a pathway that includes phosphorylation of HDAC5 and subsequent transcription of immediate-early genes (IEGs) such as Nr4a1, Fosb, Junb, Arc, Egr1, and Srf. Together, these studies suggest GRK5 is linked to T2D through regulation of ß cell growth and that it may be a target to preserve ß cells during the development of T2D.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
IScience
Año:
2023
Tipo del documento:
Article
País de afiliación:
Canadá