Abnormalities of the Exocrine Pancreas in Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is considered a pancreatic beta cell-specific disease that results in absolute insulin deficiency. Nevertheless, clinical studies from 1940 onwards showed that patients with T1D had an abnormal exocrine pancreas due to the presence of subclinical exocrine insufficiency and acinar atrophy. Exocrine abnormalities are an important, and mostly neglected, characteristic associated with T1D. It is however still unclear whether the exocrine dysfunction in T1D is a primary damage caused by the same pathogenic event that led to beta cell destruction or secondary to beta cell loss. In this review, we collect evidence supporting the hypothesis that T1D is a combined endocrine-exocrine disease in which the loss of functional beta cell mass is most clinically apparent.

Fig. 1

Exocrine and endocrine pathways to diabetes. 1-3 T3cDM. A “hit” (e.g., environmental, genetic predisposition) (1) leads to acinar injury that stimulates an inflammatory response (2) in which beta cells are lost as innocent bystanders (3). Destruction of sufficient numbers of beta cells leads to insulin deficiency and T3cDM. 4-7 Classical T1D. A “hit” (e.g., environmental, genetic predisposition) leads to beta cell inflammation, release of self antigens (4), and recruitment of immune cells (5) that target the islet leading to beta cell damage and reduced insulin production (6). Lack of insulin, which is an exocrine growth factor, leads to reduction in exocrine tissue (atrophy) (7). 8-10 Simultaneous T1D-exocrine. A “hit” (e.g., environmental) leads to pancreas inflammation (8), which attracts immune cells (9) to both endocrine and exocrine compartments and induces cellular damage (10). As a consequence, both exocrine insufficiency and insulin deficiency occur which eventually resulting in diabetes onset