A mathematical model of insulin action on acinar tissue linking histology and radiological imaging of the pancreas

The pancreas is smaller in individuals with type 1 and type 2 diabetes. The etiology of this reduced pancreatic volume is not fully understood, but it may be due to loss of insulin's trophic influence on exocrine pancreatic tissue. Supporting this, histological studies have identified a zone of acinar cell hypertrophy and hyperplasia surrounding pancreatic islets, putatively due to insulin action on peri-islet acinar tissue. This study develops a mathematical model of pancreas size incorporating beta cell density, beta cell clustering, and the magnitude and spatial extent of acinar cell expansion to estimate the relationship between beta cell mass and pancreas size. This model indicates that growth of acinar tissue surrounding the beta cell is sufficient to account for the smaller pancreas volume observed in individuals with diabetes. Furthermore, single beta cells and smaller beta cell clusters have a greater influence on pancreas size on a per cell basis, as larger islets have greater overlap in the zone of insulin action. Thus, changes in pancreas volume may be more sensitive to loss of single beta cells or small islets than larger islets. The model provides a conceptual framework linking histological and radiological imaging to better understand the relationship between pancreas volume and beta cell mass.