Promoting effects of the adipokine, apelin, on diabetic nephropathy

PLoS One. 2013;8(4):e60457. doi: 10.1371/journal.pone.0060457. Epub 2013 Apr 5.


Angiogenesis, increased glomerular permeability, and albuminuria are thought to contribute to the progression of diabetic nephropathy (DN). Apelin receptor (APLNR) and the endogenous ligand of APLNR, apelin, induce the sprouting of endothelial cells in an autocrine or paracrine manner, which may be one of the mechanisms of DN. The aim of this study was to investigate the role of apelin in the pathogenesis of DN. Therefore, we observed apelin/APLNR expression in kidneys from patients with type 2 diabetes as well as the correlation between albuminuria and serum apelin in patients with type 2 diabetes. We also measured the proliferating, migrating, and chemotactic effects of apelin on glomerular endothelial cells. To measure the permeability of apelin in glomerular endothelial cells, we used transwells to detect FITC-BSA penetration through monolayered glomerular endothelial cells. The results showed that serum apelin was significantly higher in the patients with type 2 diabetes compared to healthy people (p<0.05, Fig. 1B) and that urinary albumin was positively correlated with serum apelin (R = 0.78, p<0.05). Apelin enhanced the migration, proliferation, and chemotaxis of glomerular endothelial cells in a dose-dependent manner (p<0.05). Apelin also promoted the permeability of glomerular endothelial cells (p<0.05) and upregulated the expression of VEGFR2 and Tie2 in glomerular endothelial cells (p<0.05). These results indicated that upregulated apelin in type 2 diabetes, which may be attributed to increased fat mass, promotes angiogenesis in glomeruli to form abnormal vessels and that enhanced apelin increases permeability via upregulating the expression of VEGFR2 and Tie2 in glomerular endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / metabolism*
  • Albuminuria / complications
  • Animals
  • Apelin
  • Apelin Receptors
  • Cell Movement
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kidney Glomerulus / pathology
  • Male
  • Mice
  • Middle Aged
  • Permeability
  • Receptor, TIE-2 / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • APLN protein, human
  • APLNR protein, human
  • Adipokines
  • Apelin
  • Apelin Receptors
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-2

Grants and funding

This project was supported by the Natural Science Foundation of China (Grant No. 30900573) ,Beijing Talents Education Project and Basic–clinical cooperation foundation of Capital Medial University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.