科研之友
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摘要
The presence and location of resident pancreatic beta-cell progenitors is controversial. A subpopulation of insulin-expressing but glucose transporter-2-low (Ins(+)Glut2(LO)) cells may represent multipotent pancreatic progenitors in adult mouse and in human islets, and they are enriched in small, extra-islet beta-cell clusters (< 5 beta cells) in mice. 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 7, 14, 21, 28, and at 3, 6, 12, and 18 months of age, and in the first 28 days after beta-cell mass depletion following streptozotocin (STZ) administration. Samples of human pancreas 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 beta cells within clusters relative to that in islets was higher in pancreas of human than of mouse at all ages examined, and decreased significantly at adolescence. In mice, the total number of Ins(+)Glut2(LO) cells decreased after 7 days concurrent with the proportion of clusters. These cells were more abundant in clusters than in islets in both species. A positive association existed between the appearance of new beta cells after the STZ treatment of young mice, particularly in clusters and smaller islets, and an increased proportional presence of Ins(+)Glut2(LO) cells during early beta-cell regeneration. These data suggest that Ins(+)Glut2(LO) cells are preferentially located within beta-cell clusters throughout life in pancreas of mouse and human, and may represent a source of beta-cell plasticity.
- 出版日期2017-6
