Grant: Project Grant

We have found a unique and never-before-seen type of diabetes in a young woman who has a mutated EP300 gene. She developed diabetes at age 23 years, though she wasn't obese and didn't go into diabetic coma. Therefore she doesn't really have ordinary type 1 or type 2 diabetes: hers is a rare and interesting type of diabetes that bridges between both kinds of diabetes. We made an animal model of her diabetes by knocking the Ep300 gene out in their insulin-making cells (also known as beta cells). Mice missing the Ep300 gene in their beta cells actually have about 30% fewer of these cells than average, but the mice still get early-onset diabetes. The purpose of this research is to find out exactly which genes depend on Ep300 to work correctly. We know that Ep300 deletion might damage beta cells in various ways: by preventing them from making insulin, by stopping stem cells from birthing new beta cells, by preventing healthy beta cells from replacing themselves, and/or by increasing the rate of beta cell death. We hope to understand how normal Ep300 protein works in beta cells so that we can learn better ways to convert stem cells into working beta cells, and to prevent diabetes by making beta cells tougher and more resistant to damage. By studying this rare form of diabetes, we therefore hope to learn key lessons about the two most common types of diabetes.