ANGPTL4 participates in gestational diabetes mellitus via regulating Akt pathway

M. Li, X.-J. Yang, G.-Y. Zhang, D.-X. Su, L. Lei, R. Li

Department of Obstetrics, Jining No. 1 People’s Hospital, Jining, China. ezul07@163.com

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• Obstetrics

OBJECTIVE: To explore ANGPTL4 expressions in patients with gestational diabetes mellitus (GDM) and its underlying mechanism.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: ANGPTL4 is down-regulated in GDM and may participate in the GDM development by promoting insulin resistance and secretion of inflammatory cytokines.

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