Small things matter: Lack of extraislet β cells in type 1 diabetes
Kathryn Murrall, Teifion Luckett, Christiana Lekka, Christine S. Flaxman, Rebecca C. Wyatt, Pouria Akhbari, Irina Kusmartseva, Susan B. Hunter, Pia Leete, Isabel Burn, Elena Osokina, James Shaw, Noel G. Morgan, Sarah J. Richardson
Abstract
Recent three-dimensional (3D) analyses reported an abundance of small β cell-rich endocrine objects (EOs) in the human pancreas. Here, we used archival, immunolabeled 2D pancreas sections to assess morphological EO parameters in donors with or without type 1 diabetes (T1D), varying in age and disease duration. We confirm that abundant small, insulin-positive EOs are present in donors without diabetes and comprise most of the pancreatic endocrine area in early life. Small EOs are virtually absent in individuals with T1D, and this effect is most pronounced in children diagnosed with T1D in their earliest years. We conclude that extraislet β cells are affected in T1D development, and their early loss is a characteristic feature. This finding has important implications, which will inform future screening and treatment strategies for T1D.