Loss of Reg proteins’ protection of islet β cells in chronic pancreatitis: A potential mechanism for the pathogenesis of type 3c diabetes

Type 3c diabetes mellitus (T3cDM) is a type of pancreatogenic diabetes. This form of diabetes has been significantly underappreciated, but is now receiving increased attention because of the recent recognition of its high incidence in chronic pancreatitis (CP) and other pancreatic diseases with irreparable loss of acinar cells. CP-associated T3cDM is characterized by insulin insufficiency resulting from pancreatic exocrine damage. However, how loss of acinar cells leads to insulin insufficiency in CP is practically unknown. Based on our review of the relevant literature and studies in our laboratory, we propose that lost protection from acinar cell–secreted regenerating proteins results in injury of the islet β cells in CP. Validation of this model may help in better understanding of the pathophysiology of T3cDM.