No Compensatory Increase in Non-ß Hormone Expressing Cells in the Pancreatic Duct Glands in Type 1 Diabetes

Abstract

Longstanding type 1 diabetes (T1D) entails a near total loss of β cells secondary to autoimmunity, fibrosis and decreased total organ mass, but accumulating evidence suggests there may be an endogenous attempt to regenerate β cells. Pancreatic duct glands (PDGs) represent a distinct anatomical compartment of the pancreas, forming blind ending outpouchings from the main pancreatic duct and its branches. The PDG is purported to be a potential stem/progenitor cell niche. PDGs respond to inflammation in T1D by becoming activated, evidenced by a high frequency of epithelial cell replication and an increase in progenitor-like cells. Hence, we addressed the hypothesis that in T1D, perturbation of hormone-expressing endocrine cells in the interlobular ducts (ILD) and PDGs exist. Pancreatic sections from 10 T1D (disease duration 8-58 year) and 11 similarly aged control (ND) donors were evaluated for replication and expression of known pancreatic endocrine hormones in ducts and PDG. We confirmed increased duct and PDG replication in T1D (T1D vs. ND— ILD: 4.5 ± 1.8 vs. 0.8 ± 0.2%, p<0.05; PDG: 3.4 ± 1.3 vs. 0.4 ± 0.2%, p<0.05) and reduced frequency of insulin expressing cells (T1D vs. ND— ILD: 0.0 ± 0.0 vs. 0.4 ± 0.1%, p<0.001; PDGs: 0.± 0.07 vs. 2.4 ± 0.8%, p<0.05). No differences were found in the frequency of other known endocrine cell types (T1D vs. ND— ILD: Glucagon: 1.5 ± 0.7 vs. 2.1 ± 0.6%, Somatostatin: 1.2 ± 0.4 vs. 1.6 ± 0.3%, Pancreatic Polypeptide: 0.4 ± 0.2 vs. 1.3 ± 0.3%; PDGs: Glucagon: 0.9 ± 0.9 vs. 1.6 ± 1.0%, Somatostatin: 1.96 ± 0.8 vs. 3.7 ± 1.9%, Pancreatic Polypeptide: 1.7 ± 1.1 vs. 2.1 ± 0.8%; p=ns, all). These data suggest that increased cell replication and the deficiency of insulin expressing cells in the PDG compartment of subjects with T1D are not associated with a corresponding increase in non-insulin hormone-expressing endocrine cells. Furthermore, the consistent observation of increased cell replication in the ducts and PDGs in T1D may implicate regenerative mechanisms towards an exocrine cell fate. Disclosure S.S. Kulkarni: None. M.A. Atkinson: Other Relationship; Self; Patent Issued. A. Butler: None.