Highly Proliferative α-Cell-Related Islet Endocrine Cells inHuman Pancreata
Highly Proliferative α-Cell-Related Islet Endocrine Cells inHuman Pancreata
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DOI：
10.2337/db17-1114
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发表时间：
2018-04-01
期刊：
影响因子：
7.7
通讯作者：
Kushner, Jake A.
中科院分区：
文献类型：
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作者：
Lam, Carol J.;Cox, Aaron R.;Kushner, Jake A.
非β胰岛内分泌细胞对 1 型糖尿病 (T1D) 的增殖反应仍不清楚。我们对大量不同年龄段的非糖尿病对照组和 T1D 人类胰腺中的胰岛内分泌细胞增殖进行了定量。令人惊讶的是，许多青少年和年轻成人 T1D 胰腺中存在大量增殖的胰岛内分泌细胞。但在对照样本中，增殖性胰岛内分泌细胞也以相似的丰度存在。我们用针对各种胰岛激素的抗血清询问了增殖的胰岛细胞。尽管胰多肽、生长抑素和生长素释放肽细胞没有表现出频繁的增殖，但表达胰高血糖素的α细胞在许多青少年和年轻人样本中高度增殖。值得注意的是，α 细胞仅占这些样本中增殖胰岛细胞的一小部分（大约 1/3）；大多数增殖细胞不表达胰岛激素。增殖激素阴性细胞一致含有 ARX（指示 α 细胞命运）和细胞质 Sox9 (Sox9(Cyt)) 的免疫反应性。这些激素阴性细胞代表了大部分胰岛内分泌 Ki67+ 细胞核，并且从婴儿期到成年早期一直保守。我们的研究揭示了一个新的高度增殖的 ARX+ Sox9(Cyt) 激素阴性细胞群，并表明青少年和成人胰腺中可能存在以前未被识别的胰岛发育和/或谱系可塑性。
The proliferative response of non-beta islet endocrine cells in response to type 1 diabetes (T1D) remains undefined. We quantified islet endocrine cell proliferation in a large collection of nondiabetic control and T1D human pancreata across a wide range of ages. Surprisingly, islet endocrine cells with abundant proliferation were present in many adolescent and young-adult T1D pancreata. But the proliferative islet endocrine cells were also present in similar abundance within control samples. We queried the proliferating islet cells with antisera against various islet hormones. Although pancreatic polypeptide, somatostatin, and ghrelin cells did not exhibit frequent proliferation, glucagon-expressing alpha-cells were highly proliferative in many adolescent and young-adult samples. Notably, alpha-cells only comprised a fraction (similar to 1/3) of the proliferative islet cells within those samples; most proliferative cells did not express islet hormones. The proliferative hormone-negative cells uniformly contained immunoreactivity for ARX (indicating alpha-cell fate) and cytoplasmic Sox9 (Sox9(Cyt)). These hormone-negative cells represented the majority of islet endocrine Ki67+ nuclei and were conserved from infancy through young adulthood. Our studies reveal a novel population of highly proliferative ARX+ Sox9(Cyt) hormone-negative cells and suggest the possibility of previously unrecognized islet development and/or lineage plasticity within adolescent and adult human pancreata.