1739-P: Ontogeny of Bihormonal Islet Cells within the Human Pancreas

Bi-hormonal islet endocrine cells have been proposed to represent an intermediate state during cellular trans-differentiation, enabling plasticity of islet beta-cells in response to metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated bi-hormonal islet endocrine cell populations present throughout the human lifespan between 11 days to 79 years of age. Immunohistochemical staining was performed on paraffin-embedded sections of pancreata from 24 individuals without diabetes for insulin, glucagon, and somatostatin. The sections were imaged with epifluorescence microscopy, and hormone-positive cells were manually counted using ImageJ software considering cells where more than 50% of the area was immunopositive. The mean proportional presence of glucagon-, insulin-, and somatostatin-immunopositive cells within islets was 28.8%, 65.1%, and 13.8% respectively, similar to previous reports for human islets. The relative presence of alpha- and beta-cells increased, and for delta-cells decreased, with advancing age. With respect to bi-hormonal cells the overall presence of glucagon+/insulin+ cells was 3.3%, for somatostatin+/insulin+ cells was 2.4%, and for glucagon+/somatostatin+ cells was 1.7% relative to total islet cell number. The proportion of glucagon+/somatostatin+ cells in the islets of female individuals, in particular, diminished with age (r2=0.43), whereas the other cell types remained largely constant with age in both sexes. The prevalence of tri-hormonal islet cells was low (0.45%). The findings suggest that bi-hormonal islet cells are present within human pancreatic islets throughout life, perhaps reflecting an ongoing potential for endocrine cell plasticity.