Pharmacological modulation of prostaglandin E (PGE ) EP receptors improves cardiomyocyte function under hyperglycemic conditions.

Type 2 diabetes (T2D) affects >30 million Americans and nearly 70% of individuals with T2D will die from cardiovascular disease (CVD). Circulating levels of the inflammatory signaling lipid, prostaglandin E (PGE ), are elevated in the setting of obesity and T2D and are associated with decreased cardiac function. The EP3 and EP4 PGE receptors have opposing actions in several tissues, including the heart: overexpression of EP3 in cardiomyocytes impairs function, while EP4 overexpression improves function.

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

Objective: Type 2 diabetes is characterized by hyperglycemia and inflammation. Prostaglandin E, 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.