title: Adult-onset deletion of Pten increases islet mass and beta cell proliferation in mice.
abstract: OBJECTIVE
  Adult beta cells have a diminished ability to proliferate. Phosphatase and tensin homologue (PTEN) is a lipid phosphatase that antagonises the function of the mitogenic phosphatidylinositol 3-kinase (PI3K) pathway. The objective of this study was to understand the role of PTEN and PI3K signalling in the maintenance of beta cells postnatally.
  
  
  METHODS
  We developed a Pten (lox/lox); Rosa26 (lacZ); RIP-CreER (+) model that permitted us to induce Pten deletion by treatment with tamoxifen in mature animals. We evaluated islet mass and function as well as beta cell proliferation in 3- and 12-month-old mice treated with tamoxifen (Pten deleted) vs mice treated with vehicle (Pten control).
  
  
  RESULTS
  Deletion of Pten in juvenile (3-month-old) beta cells significantly induced their proliferation and increased islet mass. The expansion of islet mass occurred concomitantly with the enhanced ability of the Pten-deleted mice to maintain euglycaemia in response to streptozotocin treatment. In older mice (>12 months of age), deletion of Pten similarly increased islet mass and beta cell proliferation. This novel finding suggests that PTEN-regulated mechanisms may override the age-onset diminished ability of beta cells to respond to mitogenic stimulation. We also found that proteins regulating G1/S cell-cycle transition, such as cyclin D1, cyclin D2, p27 and p16, were altered when PTEN was lost, suggesting that they may play a role in PTEN/PI3K-regulated beta cell proliferation in adult tissue.
  
  
  CONCLUSIONS
  The signals regulated by the PTEN/PI3K pathway are important for postnatal maintenance of beta cells and regulation of their proliferation in adult tissues.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kai-Ting
authors.initials: KT
authors.lastname: Yang
authors.forename: Jennifer-Ann
authors.initials: JA
authors.lastname: Bayan
authors.forename: Ni
authors.initials: N
authors.lastname: Zeng
authors.forename: Richa
authors.initials: R
authors.lastname: Aggarwal
authors.forename: Lina
authors.initials: L
authors.lastname: He
authors.forename: Zhechu
authors.initials: Z
authors.lastname: Peng
authors.forename: Anketse
authors.initials: A
authors.lastname: Kassa
authors.forename: Melissa
authors.initials: M
authors.lastname: Kim
authors.forename: Zhiou
authors.initials: Z
authors.lastname: Luo
authors.forename: Zhenrong
authors.initials: Z
authors.lastname: Shi
authors.forename: Vivian
authors.initials: V
authors.lastname: Medina
authors.forename: Keerthi
authors.initials: K
authors.lastname: Boddupally
authors.forename: Bangyan L
authors.initials: BL
authors.lastname: Stiles
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D002453:Cell Cycle; D016923:Cell Death; D049109:Cell Proliferation; D019175:DNA Methylation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D017353:Gene Deletion; D006706:Homeostasis; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse