Dual Modulation of Prostaglandin E2 Receptors EP3 and EP4 Protects β-Cell Mass in a Model of Aggressive Autoimmune
Juliann B Burkett1, Jennifer Fuhr2, Alexander C Falk3
1Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN.
Article Highlights:
Modulation of prostaglandin E2 (PGE2) signaling improves β-cell health and survival. In this study, we examined whether these β-cell effects could be harnessed alongside known PGE2-mediated immunomodulation to ameliorate β-cell loss in a model of severe islet autoimmunity. Simultaneous pharmacological blockade of the EP3 receptor and activation of the EP4 receptor maintain mature β-cell mass, ameliorate the proinflammatory insulitic microenvironment, and alter β-cell stress responses in female nonobese diabetic mice undergoing aggressive inflammatory assault. EP modulation shows promise to support β-cell resiliency and reduce inflammation in a setting of autoimmune attack, such as type 1 diabetes.
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