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

Abstract

Our study highlighted a pivotal role for PLGF in prevention and treatment of GDM in patients with PE.

Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling

“…Together, these data are consistent with the previous findings in PI3k/Akt pathway, since Akt can phosphorylate FoxO1 to release FoxO1 from p21 and p27 promoter, and Akt can activate mTor to directly activate CDK4 and CyclinD1 [28,29]. Together with our previous findings [6], our studies suggest a model in that PLGFs play a key role in gestation. Reduction of PLGF may induce vascular defects that affect cardiac endothelial cells to induce hypertension and other PE-like symptoms.…”

“…Together, these data suggest that activation of PI3k/Akt signalling in beta cells may increase beta-cell proliferation through modulation of cell-cycle regulators p21, p27, CDK4 and CyclinD1. Together with our previous findings [6], the model of contribution of reduced gestational PLGF to PE and GDM has been illustrated (Fig. 5).…”

“…Recently, we reported that impairment in gestational beta-cell mass growth may result from PE-associated PLGF reduction, which may explain the pathogenesis of GDM [6]. Since the PLGF has a unique receptor, VEGFR1 or Flt-1, which exclusively expresses in the endothelial cells but not in beta cells in the islets (Fig.…”

“…Moreover, PE and GDM co-occur in many patients [1,2,3,4,5]. However, a molecular relationship between development of PE and GDM is much unknown, until recently we reported that impairment in gestational beta-cell mass growth may result from PE-associated reduction in placental growth factor (PLGF) and lead to development of GDM [6]. …”

“…Recently, we reported that impairment in gestational beta-cell mass growth may result from PE-associated PLGF reduction, which may explain the pathogenesis of GDM [6]. Since the PLGF has a unique receptor, VEGF receptor 1 (VEGFR1) or Flt-1, which exclusively expresses in the islet endothelial cells with the islets, but not in beta cells [13,14,15,16,17], we hypothesize that gestational PLGF may target islet endothelia, which release growth factors to the nearby beta cells to increase their proliferation.…”