Pancreatic tissue is composed of two dominant cell types: small clusters of insulin producing cells called the islets of Langerhans and exocrine cells in the surrounding stroma. The endocrine and exocrine pancreatic tissues are fundamentally different in terms of anatomical organization, basic function and pathological conditions, and they are consequently believed to be largely independent from each other with respect to their biological roles. Our research is based on the premise that the endocrine and exocrine pancreas do not operate in isolation, but rather have a close functional relationship that influences islets both under normal and under diabetic conditions. Specifically, we propose that crosstalk between exocrine and endocrine pancreatic tissue is dependent on islet sensing signals that are generated in the surrounding tissue – a process we hypothesize is regulated by proteases. Although proteases, and the immune response to protease inhibitors, have been implicated in the pathogenesis of inflammation and autoimmunity, studies in our laboratory suggest that an immune response to the serpin protease inhibitors and the consequent increase in protease activity is unique in that it is protective rather than pathogenic during the diabetogenic destruction of pancreatic islets.
