Endocrine Abstracts

Understanding how pancreatic beta-cells develop during human development is essential to advance current protocols aimed at developing insulin-producing beta-cells in vitro and highlight therapeutic targets for diabetes treatment. Identifying the single-gene mutations which result in individuals developing diabetes in the first 6 months of life (a condition called neonatal diabetes) has the potential to give unique insights into the genes regulating human beta-cells which would never be discovered by studying animal models alone. By performing genome sequencing analysis of >100 individuals with neonatal diabetes, we have identified mutations in genes which were not previously thought to be important within beta-cells. These include genes essential for preserving beta-cell function (like YIPF5 which encodes a regulator of endoplasmic reticulum to Golgi transport) and genes crucial for human pancreatic development (such as the gene encoding for the negative regulator of transcription and stem cell pluripotency factor, CNOT1). These results highlight the power of human genetic studies to pinpoint genes which are essential for human beta-cell function and development, improving our knowledge of the biological mechanisms leading to diabetes and highlighting new promising targets to be further investigated to develop better therapies for individuals living with diabetes.