Serum levels of advanced glycation end products (AGEs) are independently correlated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans

Clin Biochem. 2013 Mar;46(4-5):300-3. doi: 10.1016/j.clinbiochem.2012.11.023. Epub 2012 Dec 4.


Objectives: Inhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a potential therapeutic target for type 2 diabetes. Although soluble DPP-4 has been identified in human serum and could be associated with DPP-4 activity, the kinetics and regulation of circulating DPP-4 levels remain unknown. In this study, we examined which anthropometric and metabolic variables, including serum levels of advanced glycation end products (AGEs), were independently associated with serum DPP-4 levels. Further, we investigated the effects of AGEs on DPP-4 expression in, and soluble DPP-4 release from human cultured proximal tubular epithelial cells.

Design and methods: The study involved 432 consecutive outpatients (301 males and 131 females; mean ages 61.8 ± 8.8) who underwent complete history and physical examinations, and determinations of blood chemistry and anthropometric variables. Serum DPP-4 and AGE levels were examined by enzyme-linked immunosorbent assay. Protein expression levels of DPP-4 and its release from the cells were analyzed with western blot analysis.

Results: Mean serum levels of DPP-4 and AGEs were 520.2 ± 39.9 ng/mL and 8.96 ± 2.57 U/mL, respectively. In multiple regression analysis, female (p<0.001), HDL-cholesterol (p<0.001), glycated hemoglobin (p<0.001), AGEs (p<0.03), and the absence of hypertension medication (p<0.05) are independently associated with DPP-4 levels (R(2)=0.167). Western blot analysis revealed that AGEs significantly increased DPP-4 expression in, and soluble DPP-4 release from tubular cells.

Conclusions: The present study reveals that serum levels of DPP-4 are independently associated with various metabolic parameters in a general population. AGEs may up-regulate cellular DPP-4 expression and subsequently increase circulating levels of DPP-4 in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cells, Cultured
  • Cross-Sectional Studies
  • Dipeptidyl Peptidase 4 / blood*
  • Female
  • Glycation End Products, Advanced / blood*
  • Humans
  • Male
  • Middle Aged


  • Biomarkers
  • Glycation End Products, Advanced
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4