Beamish Christine A, Mehta Sofia, Strutt Brenda J, Chakrabarti Subrata, Hara Manami, Hill David J
Lawson Health Research InstituteSt Joseph Health Care, London, Ontario, Canada.
Department of Physiology & PharmacologyWestern University, London, Ontario, Canada.
J Endocrinol. 2017 Jun;233(3):229-241. doi: 10.1530/JOE-16-0475. Epub 2017 Mar 27.
The presence and location of resident pancreatic β-cell progenitors is controversial. A subpopulation of insulin-expressing but glucose transporter-2-low (InsGlut2) cells may represent multipotent pancreatic progenitors in adult mouse and in human islets, and they are enriched in small, extra-islet β-cell clusters (<5 β 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 β-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 β 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 InsGlut2 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 β cells after the STZ treatment of young mice, particularly in clusters and smaller islets, and an increased proportional presence of InsGlut2 cells during early β-cell regeneration. These data suggest that InsGlut2 cells are preferentially located within β-cell clusters throughout life in pancreas of mouse and human, and may represent a source of β-cell plasticity.
胰腺常驻β细胞祖细胞的存在及其位置存在争议。在成年小鼠和人类胰岛中，表达胰岛素但葡萄糖转运蛋白2水平较低（InsGlut2）的细胞亚群可能代表多能胰腺祖细胞，并且在小鼠的小的胰岛外β细胞簇（<5个β细胞）中富集。在这里，我们试图确定并比较这些细胞在小鼠和人类胰腺一生中的个体发生情况。在出生后第7、14、21、28天以及3、6、12和18月龄时收集小鼠胰腺，以及在注射链脲佐菌素（STZ）导致β细胞团耗竭后的前28天收集。在胎儿期（妊娠22 - 30周）、婴儿期（0 - 1岁）、儿童期（2 - 9岁）、青春期（10 - 17岁）和成年期（18 - 80岁）检查人类胰腺样本。通过免疫组织化学分析组织中胰岛素、GLUT2和Ki67的表达及位置。在所检查的所有年龄段中，人类胰腺中簇内β细胞相对于胰岛内β细胞的比例高于小鼠，且在青春期显著下降。在小鼠中，7天后InsGlut2细胞总数与细胞簇比例同时下降。在这两个物种中，这些细胞在细胞簇中比在胰岛中更丰富。在对幼鼠进行STZ治疗后新β细胞的出现，特别是在细胞簇和较小的胰岛中，与早期β细胞再生过程中InsGlut2细胞比例增加呈正相关。这些数据表明，InsGlut2细胞在小鼠和人类胰腺一生中优先位于β细胞簇内，可能代表β细胞可塑性的一个来源。
