title: Impaired proliferation of pancreatic beta cells, by reduced placental growth factor in pre-eclampsia, as a cause for gestational diabetes mellitus.
abstract: OBJECTIVE
  Reduced increase in serum placental growth factor (PLGF) levels frequently occurs in patients with pre-eclampsia (PE) and thus has been used as a predictive factor for developing PE. However, it has remained elusive how shortage of PLGF could affect pancreatic endocrine homoeostasis and function in pregnancy to lead to development of gestational diabetes mellitus (GDM).
  
  
  METHODS
  We used l-NAME injection in mice, as a model of human PE, in which PLGF levels were significantly reduced.
  
  
  RESULTS
  We not only confirmed reduced serum PLGF levels in patients with PE but also detected strong correlation of serum PLGF levels and presence of GDM. We found that growth of beta cell mass during pregnancy was significantly impaired by l-NAME injection, as a result of reduced beta cell proliferation. This may explain the higher risk of developing GDM in patients with PE. Moreover, provision of exogenous PLGF in l-NAME-treated pregnant mice significantly rescued beta cell proliferation, with subsequent increase in beta cell mass, suggesting that shortage in PLGF may be responsible for impaired beta cell growth and higher occurrence of GDM in patients with PE.
  
  
  CONCLUSIONS
  Our study highlighted a pivotal role for PLGF in prevention and treatment of GDM in patients with PE.
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Huanchun
authors.initials: H
authors.lastname: Ying
authors.forename: Guiyang
authors.initials: G
authors.lastname: Cai
authors.forename: Quan
authors.initials: Q
authors.lastname: Guo
authors.forename: Lizhu
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016640:Diabetes, Gestational / Q000209:etiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000473:pathology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood* / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy
chemical_list: D004791:Enzyme Inhibitors; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester