Pilot electron microscopy studies revealed the cellular mixing of acinar cells from the exocrine pancreas, which produce digestive enzymes, with the endocrine cells within the islets of Langerhans in the early stages of T1D in both human patient material (manuscript in preparation) and a T1D rat model (Scotuzzi et al. 2017). The cause of this endocrine-exocrine cell mixing is unknown. Moreover, T1D patients have a reduced pancreas organ weight, which cannot be explained only by the loss of islets, since islets comprise just a few percent of the total pancreas. Furthermore, increased immune cell infiltrates have been found in the exocrine pancreas, suggesting a role for the exocrine pancreas in the pathogenesis of T1D.
Interactions between the exocrine and endocrine pancreas in the development of T1D have gained increasing attention, and include reports on immune infiltrates in the exocrine pancreas during T1D and a reduced total pancreatic weight in T1D patients compared to controls (Campbell-Thompson, Rodriguez-Calvo, and Battaglia 2015; Campbell-Thompson et al. 2016). We hypothesize that initial damage to exocrine cells in the pancreas causes the release of (auto)digestive proteins, which subsequently trigger beta cell stress that ultimately result in an autoimmune response that is characteristic for T1D.