Understanding sex differences in beta-cell resilience to stresses in type 1 diabetes

Type 1 diabetes (T1D) involves the loss of insulin-secreting beta-cells, the main cell type in the pancreatic islets. A special feature of beta-cells is that they must make large quantities of insulin protein, which is very demanding and leaves them vulnerable to stress. Stressed islets are less functional and may die. Islets from females appear more resilient than islets from males to stresses relating to insulin production. However, we lack knowledge on how female islet cells achieve this, and preclinical research rarely studies both sexes. This project will characterise the mechanisms that occur in male and female islets in response to T1D-related stresses. We will generate and analyse large datasets to identify key stress response events in mouse and human donor islets. Results will be presented at scientific conferences. By understanding these mechanisms, we will likely identify therapeutic targets that can lead to future drug and cell therapies for T1D. A focus on sex differences is also key to ensuring appropriate research translation to a wider population. Finally, a fundamental understanding of sex differences in protein synthesis has implications for studies in other cells and organs, as all cells need to make protein.