Type 1 diabetes occurs when an abnormal autoimmune response destroys the β cells, a specialized group of insulin-producing cells, in the pancreas. Insulin is required to promote proper uptake and utilization of glucose, and its absence in Type 1 diabetes leads to the characteristic high blood sugar along with a range of metabolic derangements and eventually tissue damage. Current treatment of Type 1 diabetes focuses on replacing insulin by injection, but a much more satisfactory result would be achieved if it were possible to replace the missing β cells. Now, Vanderbilt Basic Sciences researchers Mark Magnuson and Guoqiang Gu and their laboratories report progress toward that goal. They created genetically altered mice that express three transcription factors known to promote β cell differentiation in the pancreas. They discovered that high expression of these three factors led to inflammation, and although many cells exhibited altered morphology and protein expression, no insulin-producing cells developed. However, when the researchers took care to prevent the inflammation, either by reducing the expression of the transcription factors or treating the mice to reduce the number of inflammatory macrophages, new cells with the characteristics of β cells developed. In addition, diabetic mice treated this way displayed a temporary improvement in their condition for as long as the transcription factors were expressed. The findings provide important insights into parameters that affect β cell reprogramming in the pancreas and help to lay the groundwork for better approaches to treatment of Type 1 diabetes in the future. The work is published in the journal Cell Reports [H. W. Clayton, et al. (2016) Cell Rep., 17, 2028].