Therapeutic Targets for Diabetes

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Type 2 diabetes results in impaired function and reduced numbers of insulin-producing beta cells in the pancreas. Proteins with roles in beta-cell proliferation and survival are attractive targets for diabetes therapies.

Maureen Gannon, Ph.D., and colleagues previously found that FoxM1, a transcription factor that promotes beta-cell proliferation and survival, regulates expression of the prostaglandin E2 receptors EP3 and EP4. The investigators have now assessed the roles of EP3 and EP4 in isolated mouse and human pancreatic islets.

They report that the two receptors have opposing roles and that blocking EP3 while activating EP4 enhances human (but not mouse) beta-cell proliferation. They further demonstrated that the positive effects of FoxM1 activation on beta-cell survival are inhibited by EP3 and dependent on EP4 signaling.

The findings, reported in Molecular Metabolism, identify EP3 and EP4 as novel regulators of beta-cell proliferation and survival and highlight these receptors as potential targets for the treatment of type 2 diabetes.

This work was supported by the Department of Veterans Affairs (grants BX000990, BX003744), the Program in Developmental Biology, and the ADI IsletCore Visiting Scientist Award.