title: Poly (ADP-ribose) transferase/polymerase-1-deficient mice resistant to age-dependent decrease in β-cell proliferation.
abstract: 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.
authors.affiliation: Department of Endocrinology, Shandong University, Qilu Hospital, Jinan, Shandong, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin-Guo
authors.initials: XG
authors.lastname: Hou
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Qin
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zhang
mesh_terms: D000222:Adaptation, Physiological; D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D048429:Cell Size; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D051847:Lithostathine / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D051847:Lithostathine; D009363:Neoplasm Proteins; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C546117:REG4 protein, mouse; C497615:Reg1 protein, mouse; C490253:Reg3b protein, mouse; D013311:Streptozocin; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005947:Glucose