Pharmacological blockade of the EP3 prostaglandin E₂ receptor in the setting of type 2 diabetes enhances β-cell proliferation and identity and relieves oxidative damage.

ABSTRACT:

Objective

Type 2 diabetes is characterized by hyperglycemia and inflammation. Prostaglandin E₂, which signals through four G protein-coupled receptors (EP1-4), is a mediator of inflammation and is upregulated in diabetes. We have shown previously that EP3 receptor blockade promotes β-cell proliferation and survival in isolated mouse and human islets ex vivo. Here, we analyzed whether systemic EP3 blockade could enhance β-cell mass and identity in the setting of type 2 diabetes using mice with a spontaneous mutation in the leptin receptor (Lepr^db).

Methods

Four- or six-week-old, db/+, and db/db male mice were treated with an EP3 antagonist daily for two weeks. Pancreata were analyzed for α-cell and β-cell proliferation and β-cell mass. Islets were isolat

SUBMITTER: Bosma KJ 

PROVIDER: S-EPMC8529552 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature