标题:Poly (ADP-ribose) transferase/polymerase-1-deficient mice resistant to age-dependent decrease in β-cell proliferation.
作者:Gong L.; Liu F.Q.; Wang Y.; Hou X.G.; Zhang W.; Qin W.D.; Zhang Y.; Chen L.;等
作者机构:[Gong, L] Department of Endocrinology, Shandong University, Qilu Hospital, Jinan, Shandong, People's Republic of China.
通讯作者地址:Gong, L.
来源:Molecular medicine (Cambridge, Mass.)
出版年:2012
卷:18
页码:816-824
摘要:Basal and adaptive β-cell regeneration capacity declines with old age, but the underlying molecular mechanisms remain incompletely understood. Poly (adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP-1) is considered a multifunctional enzyme and transcription factor that regulates pancreatic β-cell death, regeneration and insulin secretion. We analyzed the capacity of β-cell regeneration in 2-month-old (young) and 12-month-old (old) wild-type (WT) and PARP-1-/- mice before and after low-dose streptozotocin (STZ), a stimulus of β-cell regeneration and the underlying mechanism. Before STZ administration, young WT and PARP-1-/- mice showed similar β-cell proliferation. By contrast, old WT but not old PARP-1-/- mice showed severely restricted β-cell proliferation. In further assessment of the adaptive β-cell regeneration capacity with age, we observed that with a single low dose of STZ, young WT and PARP-1-/- mice showed a similar increase in β-cell proliferation, with few changes in old WT mice. Surprisingly, adaptive β-cell proliferation capacity was significantly higher in old PARP-1-/- mice than old WT mice after STZ administration. The ability of β-cell mass to expand was associated with increased levels of the regenerating (Reg) genes RegI and RegII but not RegIV. Therefore, PARP-1 is a key regulator in β-cell regeneration with advancing age in mice.
收录类别:SCOPUS;SCOPUS
Scopus被引频次:2
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84891667718&partnerID=40&md5=f5422b9b4211e4d1f243a32ac0a4c3c5
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