Investigation of Ephrin-A Reverse Signaling in Pancreatic Islets

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We have shown that beta cells in the mouse and human pancreas strongly express ephrin-A1 and ephrin-A5. Ephrin-A5-deficient mice have a defective glucose tolerance and decreased glucose-stimulated insulin secretion, showing that ephrin-A5 is required for normal insulin secretion. Conversely, activation of ephrin-A reverse signaling via EphA5-Fc fusion proteins strongly increases insulin secretion from mouse and human pancreatic islets as well as mouse insulinoma cells (MIN6). Our results therefore suggest that ephrin-A reverse signaling may play a role in diabetes and might be useful for diabetes treatment in humans. To continue this project, we would like to identify and characterize the components of this signaling pathway in pancreatic beta cells. We want to understand the role of ephrin-A1 in insulin secretion as well as uncover the mechanisms by which ephrin-As stimulate insulin secretion.