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Published on: February 28, 2013
ANGPTL4 participates in gestational diabetes mellitus via regulating Akt pathway
1Department of Obstetrics, Jining No. 1 People's Hospital, Jining, China. ezul07@163.com.
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.
Insights
Angiopoietin-like 4 (ANGPTL4) is reduced in gestational diabetes mellitus (GDM). Lower ANGPTL4 levels may drive GDM by increasing insulin resistance and inflammatory cytokine secretion.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Molecular Biology
Background:
- Gestational diabetes mellitus (GDM) is a significant pregnancy complication.
- The role of Angiopoietin-like 4 (ANGPTL4) in GDM pathogenesis is not fully understood.
Purpose of the Study:
- To investigate ANGPTL4 expression levels in GDM patients.
- To elucidate the underlying mechanisms of ANGPTL4's involvement in GDM.
Main Methods:
- Serum ANGPTL4 levels were measured in GDM patients and healthy pregnant women.
- In vitro studies using 3T3-L1 cells assessed the impact of ANGPTL4 knockdown on apoptosis, proliferation, cell cycle, glucose uptake, and adipocyte differentiation.
- Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot were used to analyze cytokine secretion and key signaling pathways (NF-kB, Akt).
Main Results:
- ANGPTL4 was found to be down-regulated in the serum of GDM patients.
- Reduced ANGPTL4 inhibited apoptosis and promoted proliferation in 3T3-L1 cells.
- Down-regulated ANGPTL4 impaired glucose uptake and the Akt pathway.
- ANGPTL4 did not significantly affect cell cycle or adipocyte differentiation.
- Decreased ANGPTL4 led to increased inflammatory cytokine secretion and activation of the NF-kB pathway.
Conclusions:
- ANGPTL4 is down-regulated in GDM.
- Reduced ANGPTL4 may contribute to GDM development by promoting insulin resistance and inflammatory cytokine release.
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