Exocrine and Endocrine Inflammation Increases Cellular Replication in the Pancreatic Duct Compartment in Type 1 Diabetes

Shweta Kulkarni; Amanda L Posgai; Irina Kusmartseva; Clive H Wasserfall; Mark A Atkinson; Alexandra E Butler

doi:10.1210/jendso/bvac136

Exocrine and Endocrine Inflammation Increases Cellular Replication in the Pancreatic Duct Compartment in Type 1 Diabetes

J Endocr Soc. 2022 Sep 3;6(11):bvac136. doi: 10.1210/jendso/bvac136. eCollection 2022 Oct 11.

Authors

Shweta Kulkarni¹, Amanda L Posgai¹, Irina Kusmartseva¹, Clive H Wasserfall¹, Mark A Atkinson^{1

2}, Alexandra E Butler³

Affiliations

¹ Department of Pathology, Immunology, and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL 32611, USA.
² Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL 32611, USA.
³ Department of Research, Royal College of Surgeons in Ireland-Bahrain, 15503 Adliya, Bahrain.

Abstract

Context: We recently demonstrated increased cellular proliferation in the pancreatic ductal gland (PDG) compartment of organ donors with type 1 diabetes, suggesting that PDGs may harbor progenitor cells capable of pancreatic regeneration.

Objective: We evaluated the impact of diabetes and pancreatic inflammation on PDG and interlobular duct (ILD) cellular proliferation and profiles.

Methods: Endocrine hormone expression (insulin, glucagon, somatostatin, pancreatic polypeptide) and proliferating Ki67+ cells were localized within the PDG and ILD compartments by multicolor immunohistochemistry in cross-sections from the head, body, and tail regions of pancreata from those with (n = 31) or without type 1 diabetes (n = 43). Whole-slide scanned images were analyzed using digital pathology.

Results: Type 1 diabetes donors with insulitis or histologically identified pancreatitis had increased cellular replication in the ILD and PDG compartments. Interestingly, while cellular proliferation within the pancreatic ductal tree was significantly increased in type 1 diabetes (PDG mean = 3.36%, SEM = 1.06; ILD mean = 2.78%, SEM = 0.97) vs nondiabetes(ND) subjects without pancreatic inflammation (PDG mean = 1.18%, SEM = 0.42; ILD mean = 0.74%, SEM = 0.15, P < 0.05), robust replication was also observed in ND donors with pancreatitis (PDG mean = 3.52%, SEM = 1.33; ILD mean = 2.18%, SEM = 0.54, P < 0.05). Few polyhormonal cells were present in the ILD (type 1 diabetes = 0.04 ± 0.02%; ND = 0.08 ± 0.03%, P = 0.40) or PDG compartment (type 1 diabetes = 0.02 ± 0.01%; ND = 0.08 ± 0.13%, P = 0.63).

Conclusion: These data suggest that increased pancreatic ductal cell replication is associated with sustained pancreatic inflammation; however, as replicating cells were hormone-negative, PDGs do not appear to represent a compelling endogenous source of hormone-positive endocrine cells.

Keywords: cellular replication; inflammation; insulitis; interlobular duct; pancreatic duct glands; pancreatitis; type 1 diabetes.

Abstract

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