Decrease in Ins+Glut2LO{beta}-cells with advancing age in mouse and human pancreas

The presence and location of resident pancreatic β-cell progenitors is controversial. A subpopulation of insulin-expressing but glucose transporter-2-low (Ins+Glut2LO) cells may represent multipotent pancreatic progenitors in adult mouse and human islets, and in mice are enriched in small, extra-islet β-cell clusters (<5 β-cells). Here, we sought to identify and compare the ontogeny of these cells in mouse and human pancreata throughout life. Mouse pancreata were collected at postnatal days (d) 7, 14, 21, 28, and at 3, 6, 12, and 18 months of age, and in the first 28 days after β-cell mass depletion following Streptozotocin (STZ) administration. Human pancreas samples were examined during fetal life (22-30 weeks gestation), infancy (0-1 year), childhood (2-9), adolescence (10-17), and adulthood (18-80). Tissues were analyzed by immunohistochemistry for the expression and location of insulin, glut2, and ki67. The proportion of β-cells within clusters relative to islets was higher in human pancreas than mouse at all ages examined, and decreased significantly at adolescence. In mice, the total number of Ins+Glut2LO cells decreased after 7 d, concurrent with the proportion of clusters. These cells were more abundant in clusters than islets in both species. A positive association existed between the appearance of new β-cells after STZ treatment of young mice, particularly in clusters and smaller islets, and an increased proportional presence of Ins+Glut2LO cells during early β-cell regeneration. These data suggest that Ins+Glut2LO cells are preferentially located within β-cell clusters throughout life in mouse and human pancreas, and may represent a source of β-cell plasticity.

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