Slow and steady is the key to β-cell replication

被引:23
作者
Brennand, Kristen
Melton, Doug [1 ]
机构
[1] HHMI, Cambridge, MA 02138 USA
关键词
beta-cell replication; diabetes; pancreatic stem cells; EMBRYONIC STEM-CELLS; GROWTH-FACTOR-ALPHA; DEPENDENT INSULINOTROPIC POLYPEPTIDE; INCREASED METABOLIC DEMAND; EXOCRINE PANCREATIC-CELLS; HOMEODOMAIN PROTEIN IDX-1; IN-VITRO DIFFERENTIATION; ISLET PRECURSOR CELLS; LEPTIN RECEPTOR GENE; ADULT-MOUSE PANCREAS;
D O I
10.1111/j.1582-4934.2008.00635.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Diabetes is a chronic disease of failed glucose homeostasis Structure and function of the adult pancreas Diabetes is an attractive target for cellular replacement therapy In vitro differentiation of beta-cells from embryonic stem cells beta-cell maintenance and expansion Strong evidence that new beta-cells come from old beta-cells All beta-cells contribute equally to islet growth and maintenance Putative pancreatic stem cells Reported evidence for bone marrow stem cells giving rise to beta-cells Reported evidence for spleen stem cells giving rise to beta-cells Reported evidence for ductal stem cells giving rise to beta-cells Reported evidence for acini stem cells giving rise to beta-cells Reported evidence for islet and/or pancreatic stem cells giving rise to beta-cells beta-cell turnover beta-cell mass is dynamic beta-cell replication changes with age beta-cell replication increases during pregnancy beta-cell replication increases in cases of increased blood glucose and/or insulin resistance beta-cell replication is regulated by cell cycle genes The elusive circulating beta-cell growth factor Increasing beta-cell replication in vivo In vitro culture of beta-cells Summary The beta-cells of the pancreas are responsible for insulin production and their destruction results in type I diabetes. beta-cell maintenance, growth and regenerative repair is thought to occur predominately, if not exclusively, through the replication of existing beta-cells, not via an adult stem cell. It was recently found that all beta-cells contribute equally to islet growth and maintenance. The fact that all beta-cells replicate homogeneously makes it possible to set up straightforward screens for factors that increase beta-cell replication either In vitro or in vivo. It is possible that a circulating factor may be capable of increasing beta-cell replication or that intrinsic cell cycle regulators may affect beta-cell growth. An improved understanding of the in vivo maintenance and growth of beta-cells will facilitate efforts to expand beta-cells In vitro and may lead to new treatments for diabetes.
引用
收藏
页码:472 / 487
页数:16
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