Highly Proliferative α-Cell-Related Islet Endocrine Cells in Human Pancreata.
Autor: | Lam CJ; McNair Medical Institute, Baylor College of Medicine, Houston, TX.; Diabetes and Endocrinology, Texas Children's Hospital, Houston, TX., Cox AR; McNair Medical Institute, Baylor College of Medicine, Houston, TX jake.kushner@mac.com racox@bcm.edu.; Diabetes and Endocrinology, Texas Children's Hospital, Houston, TX., Jacobson DR; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA., Rankin MM; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA., Kushner JA; McNair Medical Institute, Baylor College of Medicine, Houston, TX jake.kushner@mac.com racox@bcm.edu. |
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Jazyk: | angličtina |
Zdroj: | Diabetes [Diabetes] 2018 Apr; Vol. 67 (4), pp. 674-686. Date of Electronic Publication: 2018 Jan 11. |
DOI: | 10.2337/db17-1114 |
Abstrakt: | The proliferative response of non-β 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 α-cells were highly proliferative in many adolescent and young-adult samples. Notably, α-cells only comprised a fraction (∼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 α-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. (© 2018 by the American Diabetes Association.) |
Databáze: | MEDLINE |
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