ANGPTL4 participates in gestational diabetes mellitus via regulating Akt pathway.

Abstract

To explore ANGPTL4 expressions in patients with gestational diabetes mellitus (GDM) and its underlying mechanism. We first detected serum expressions of ANGPTL4 in GDM patients and healthy pregnancies. Subsequently, effects of ANGPTL4 knockdown on apoptosis, proliferation, and cell cycle in 3T3-L1 cells were determined, respectively. Effects of ANGPTL4 on glucose uptake and adipocyte differentiation were also evaluated, respectively. The cytokine secretion in adipocytes transfected with sh-ANGPTL4 was detected by quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Furthermore, effects of ANGPTL4 knockdown on NF-kB and Akt pathway were detected by Western blot. ANGPTL4 was down-regulated in serum of GDM patients. In vitro experiments suggested that down-regulated ANGPTL4 inhibited apoptosis and promoted proliferation of 3T3-L1 cells. Meanwhile, down-regulated ANGPTL4 significantly inhibited glucose uptake and Akt pathway. However, ANGPTL4 expression did not affect cell cycle and adipocyte differentiation. Detection of inflammatory cytokines suggested that down-regulated ANGPTL4 resulted in increased expressions of inflammatory cytokines and activation of NF-kB pathway. ANGPTL4 is down-regulated in GDM and may participate in the GDM development by promoting insulin resistance and secretion of inflammatory cytokines.