ANGPTL4 participates in gestational diabetes mellitus via regulating Akt pathway

Eur Rev Med Pharmacol Sci. 2018 Aug;22(16):5056-5062. doi: 10.26355/eurrev_201808_15697.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adult
  • Angiopoietin-Like Protein 4 / deficiency
  • Angiopoietin-Like Protein 4 / genetics
  • Angiopoietin-Like Protein 4 / metabolism*
  • Animals
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / metabolism*
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Insulin Resistance / physiology
  • Male
  • Mice
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology*

Substances

  • ANGPTL4 protein, human
  • Angiopoietin-Like Protein 4
  • Inflammation Mediators
  • Proto-Oncogene Proteins c-akt