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Angiopoietin-like protein 4 induces growth hormone variant secretion and aggravates insulin resistance during pregnancy, linking obesity to gestational diabetes mellitus.
Kuo, Chun-Heng; Wang, Shu-Huei; Juan, Hsien-Chia; Chen, Szu-Chi; Kuo, Ching-Hua; Kuo, Han-Chun; Lin, Shin-Yu; Li, Hung-Yuan.
Afiliación
  • Kuo CH; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Wang SH; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Juan HC; Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Chen SC; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Kuo CH; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Kuo HC; Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan.
  • Lin SY; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Li HY; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
Biofactors ; 2024 May 17.
Article en En | MEDLINE | ID: mdl-38760159
ABSTRACT
Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A-sub-E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose-response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone-variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin-mediated glucose uptake through the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases 1/2 (ERK 1/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI0,120 in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biofactors Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biofactors Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos