Aims/hypothesis
Recent histological analysis of pancreases obtained from patients with long-standing type 1 diabetes identified chronic islet
inflammation and limited evidence suggestive of beta cell replication. Studies in rodent models also suggest that beta cell
replication can be induced by certain inflammatory cytokines and by gastrin. We therefore tested the hypothesis that beta
cell replication is observed in non-autoimmune human pancreatic disorders in which localised inflammation or elevated gastrin
levels are present.
Methods
Resected operative pancreatic specimens were obtained from patients diagnosed with primary adenocarcinoma (with or without
chronic severe pancreatitis) or gastrinoma. Additional pancreatic tissue was obtained from autopsy control patients. Immunohistochemistry
was used to assess fractional insulin area, beta cell number and replication rate and differentiation factors relevant to
beta cell development.
Results
Fractional insulin area was similar among groups. Patients with pancreatic adenocarcinoma and localised chronic severe pancreatitis
displayed significant increases in the number of single beta cells, as well as increased beta cell replication rate and levels
of neurogenic differentiation 1 in islets. Patients with gastrinoma demonstrated significant increases in the number of single
beta cells, but the beta cell replication rate and islet differentiation factor levels were similar to those in the control
group.
Conclusions/interpretation
These findings indicate that chronic severe pancreatic inflammation can be associated with significant effects on beta cell
number or replication rate, depending on the distribution of the cells. This information may prove useful for attempts seeking
to design therapies aimed at inducing beta cell replication as a means of reversing diabetes.
Keywords Beta cells - Beta cell replication - Chronic pancreatitis - Gastrinoma - Islets of Langerhans - Pancreatic adenocarcinoma