posted on 2020-10-21, 18:16authored byAda AdminAda Admin, Liping Qiao, Sarah Saget, Cindy Lu, William W. Hay, Jr., Gerard Karsenty, Jianhua Shao
Hypoadiponectinemia is a risk factor of gestational diabetes mellitus (GDM).
Our previous study reported that adiponectin gene knockout mice (Adipoq-/-) develop GDM due to
insulin insufficiency. The main objective of this study was to elucidate the underlying
mechanism through which adiponectin controls islet expansion during pregnancy. A
significant reduction in β-cell proliferation rates, β-cell areas, and blood
insulin concentrations was detected in Adipoq-/-
mice at mid-pregnancy. Surprisingly, conditionally knocking down adiponectin
receptor 1 (AdipoR1) or AdipoR2 genes in β-cells during pregnancy
did not reduce β-cell proliferation rates or blood insulin concentrations. In
vitro adiponectin treatment also failed to show any effect on β-cell
proliferation of isolated pancreatic islets. It was reported that placental
lactogen (PL) plays a crucial role in pregnancy-induced maternal β-cell
proliferation. A significant decrease in phosphorylation of signal transducer and
activator of transcription 5, a downstream molecule of PL signaling, was
observed in islets from Adipoq-/-
dams. The mRNA levels of mouse PL genes were robustly decreased in the
placentas of Adipoq-/-
dams. In contrast, adiponectin treatment increased PL expression in human
placenta explants and JEG3 trophoblast cells. Most importantly, bovine PL
injection restored β-cell proliferation and blood insulin concentrations in Adipoq-/- dams. Together,
these results demonstrate that adiponectin plays a vital role in
pregnancy-induced β-cell proliferation by promoting PL expression in
trophoblast cells.
Funding
This work was supported by NIH grants DK095132 (J.S.) and DK113007 (J.S.)