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

Abstract

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.

• Authors: Nobuhiro Tahara, Sho-ichi Yamagishi, Masayoshi Takeuchi, Atsuko Tahara, Kumiko Kaifu, Seiji Ueda, Seiya Okuda, Tsutomu Imaizumi
• Journal: Clinical biochemistry (Clin Biochem) Vol. 46 Issue 4-5 Pg. 300-3 (Mar 2013) ISSN: 1873-2933 [Electronic] United States
• PMID: 23219738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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