Impaired proliferation of pancreatic beta cells, by reduced placental growth factor in pre-eclampsia, as a cause for gestational diabetes mellitus.

Abstract

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). We used l-NAME injection in mice, as a model of human PE, in which PLGF levels were significantly reduced. 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. Our study highlighted a pivotal role for PLGF in prevention and treatment of GDM in patients with PE.