Diabetes is a syndrome defined by high blood glucose levels caused by either reduction in number of insulin- producing cells (Type 1 diabetes), or the ability of our cells to respond to insulin in combination with declined numbers of insulin-producing cell number (Type 2 diabetes). Thus, a cure for diabetes should entail replacement of insulin-producing β-cells. There have been tremendous efforts throughout the years to generate β-cells from different sources, not only from embryonic stem cells, and adult stem or somatic cells, but also from non-β-cells residing in the pancreas. One such cell type is the amylase-producing pancreatic acinar cell. These cells are primarily responsible for producing and secreting enzymes that would help us digest of the food we eat. The acinar cells also represent the majority of cells in the pancreas, thus they are perfect as the source for new β-cell generation. Here, we provide evidence that both genetic as well as pharmacological inactivation of focal adhesion kinase (FAK) converts pancreatic acinar cells into insulin-producing cells in vivo. The acinar-derived insulin-producing (ADIP) cells invade the preexisting islets and are able to restore normoglycemia in non-autoimmune diabetic mice. In the current proposal, we will determine whether ADIP cells can survive, be functional and prevent diabetes in an autoimmune setting. The overall goal of this project is to determine the ability of ADIP cells to survive and avoid autoimmune attack. As a first step, we will study the effect of FAKi on T cells (aim 1). Next, we will determine whether ADIP cells can escape autoimmune T cell attack (aim 2). Finally, we will compare the expression profile of ADIP cells compared to regular β-cells (aim 3). This work is a high priority area as it is directly applicable to our full understanding and potential treatment of Type 1 and Type 2 diabetes, and may provide a key understanding of how to generate new functional β-cells from acinar cells. This procedure may result in reversal of diabetes without islet transplantation and immune suppression. More importantly, if successful, it should position us well in preparation for clinical trials in humans with diabetes.