title: Survivin is required for beta-cell mass expansion in the pancreatic duct-ligated mouse model.
abstract: OBJECTIVE
  Pancreatic beta-cell mass expands through adulthood under certain conditions. The related molecular mechanisms are elusive. This study was designed to determine whether surviving (also known as Birc5), which is transiently expressed perinatally in islets, was required for beta-cell mass expansion in the pancreatic duct-ligated mouse model.
  
  
  METHODS
  Mice with beta cell-specific deletion of survivin (RIPCre(+)survivin(fl/fl)) and their control littermates (RIPCre(+)survivin(+/+)) were examined to determine the essential role of survivin in partial pancreatic duct ligation (PDL)-induced beta-cell proliferation, function and survival.
  
  
  RESULTS
  Resurgence of survivin expression occurred as early as day 3 post-PDL. By day 7 post-PDL, control mice showed significant expansion of beta-cell mass and increase in beta-cell proliferation and islet number in the ligated tail of the pancreas. However, mice deficient in beta-cell survivin showed a defect in beta-cell mass expansion and proliferation with a marked attenuation in the increase of total islet number, largely due to an impairment in the increase in number of larger islets while sparing the increase in number of small islets in the ligated tail of pancreas, resulting in insufficient insulin secretion and glucose intolerance. Importantly however, beta cell neogenesis and apoptosis were not affected by the absence of survivin in beta cells after PDL.
  
  
  CONCLUSIONS
  Our results indicate that survivin is essential for beta-cell mass expansion after PDL. Survivin appears to exhibit a preferential requirement for proliferation of preexisting beta cells.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. drxhwu@njmu.edu.cn
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.forename: Qinfeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Jiayu
authors.initials: J
authors.lastname: Zhu
authors.forename: Kuangfeng
authors.initials: K
authors.lastname: Xu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okada
authors.forename: Rennian
authors.initials: R
authors.lastname: Wang
authors.forename: Minna
authors.initials: M
authors.lastname: Woo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D017353:Gene Deletion; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008026:Ligation; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010183:Pancreatic Ducts; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D007328:Insulin; D012097:Repressor Proteins; D000077022:Survivin