by Leigh MacMillan
Type 2 diabetes is characterized by chronic hyperglycemia (high blood glucose) and inflammation, which are associated with increased levels of circulating prostaglandin E2 (PGE2) — a mediator of inflammation.
Maureen Gannon, PhD, and colleagues previously showed that blocking one of the PGE2 receptors, EP3, promoted insulin-secreting beta-cell proliferation and survival in isolated mouse and human pancreatic islets. Now, the researchers extend these studies in vivo, using a mouse model of type 2 diabetes (db/db).
They found that systemic EP3 blockade increased beta-cell proliferation and mass in db/db mice, reversed changes in islet gene expression associated with the db/db phenotype, and restored islet architecture. They also discovered increased expression of GLP-1R, a therapeutic target for type 2 diabetes, and Nrf2, which protects against cellular oxidative damage.
The findings, reported in Molecular Metabolism, show that blocking EP3 activity improves beta-cell characteristics in a mouse model of type 2 diabetes and may provide added benefits to GLP-1R medications.
VUMC postdoctoral fellows Karin Bosma, PhD, and Spencer Andrei, PhD, are co-first authors of the current study. The research was supported by the National Institutes of Health (grants DK020593, CA119925, DK007563, DK127613, DK102598, DK120626, DK114338, HL134895, AG065859, AG063217) and Department of Veterans Affairs Merit Review awards.
