Retinoblastoma tumor suppressor protein in pancreatic progenitors controls alpha- and beta-cell fate

作者：Cai Erica P; Wu Xiaohong; Schroer Stephanie A; Elia Andrew J; Nostro M Cristina; Zacksenhaus Eldad; Woo Minna^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(36): 14723-14728.

DOI：10.1073/pnas.1303386110

• diabetes mellitus
• insulin
• glucagon
• cell cycle
• E2f

Pancreatic endocrine cells expand rapidly during embryogenesis by neogenesis and proliferation, but during adulthood, islet cells have a very slow turnover. Disruption of murine retinoblastoma tumor suppressor protein (Rb) in mature pancreatic beta-cells has a limited effect on cell proliferation. Here we show that deletion of Rb during embryogenesis in islet progenitors leads to an increase in the neurogenin 3-expressing precursor cell population, which persists in the postnatal period and is associated with increased beta-cell mass in adults. In contrast, Rb-deficient islet precursors, through repression of the cell fate factor aristaless related homeobox, result in decreased alpha-cell mass. The opposing effect on survival of Rb-deficient alpha- and beta-cells was a result of opposing effects on p53 in these cell types. As a consequence, loss of Rb in islet precursors led to a reduced alpha- to beta-cell ratio, leading to improved glucose homeostasis and protection against diabetes.

• 出版日期2013-9-3
• 单位南京医科大学; 河北医科大学