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

Dipeptidyl peptidase-4 deficiency protects against experimental diabetic nephropathy partly by blocking the advanced glycation end products-receptor axis

“…18 Further, serum DPP-4 levels were significantly increased in STZ rats, 18 and AGEs levels were independently correlated with circulating levels of DPP-4 in humans. 23 These observations could indicate the pathological crosstalk between the AGE-RAGE axis and DPP-4 in vascular injury of diabetes, thus suggesting that inhibition of DPP-4 by linagliptin might have glucoselowering-independent, beneficial actions on experimental diabetic nephropathy. However, it remains unclear whether DPP-4 deficiency could also exert pleiotropic effects on diabetic nephropathy of STZ rats, a model of type 1 diabetic animal.…”

Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes

“…So far, we have found that glyceraldehyde-derived AGE levels are (a) correlated with a soluble form of RAGE that could reflect tissue RAGE expression in both nondiabetic and diabetic subjects (104)(105)(106)(107), thus suggesting a marker of the activation of AGE-RAGE axis; (b) associated with low-density lipoprotein cholesterol levels and thrombogenic markers such as plasminogen activator inhibitor-1 and fibrinogen in a general population (108)(109)(110); (c) elevated under oxidative stress, chronic kidney disease and/or diabetic conditions and corre-lated with inflammatory biomarkers such as monocyte chemoattractant protein-1, the soluble form of vascular cell adhesion molecule-1 and ADMA (106,107,(111)(112)(113); (d) increased in nonalcoholic steatohepatitis (NASH) patients and associated with insulin resistance in both NASH subjects and an non-NASH general population (114)(115)(116); (e) correlated with serum PEDF and DPP-4 levels, markers of insulin resistance (117,118); (f) associated with visceral and subcutaneous adipose tissue inflammation and decreased adiponectin levels (114,119); (g) correlated with vascular inflammation and endothelial dysfunction in high-risk patients (120,121); (h) inversely associated with number and migratory activity of EPCs (122), thus suggesting the involvement of this type of AGEs in impaired endothelial cell repair; and (i) significantly associated with plaque progression in patients with acute coronary syndrome (123). Moreover, atrovastatin, pioglitazone and α-glucosidase inhibitor have been shown to significantly decrease serum levels of glyceraldehyde-derived AGEs, which are associated with reduced biomarker levels for organ damage in diabetic, chronic kidney disease or NASH subjects (120,(124)(125)(126)(127)(128).…”

Serum levels of pigment epithelium-derived factor (PEDF) are inversely associated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans

“…The study involved 188 subjects (123 males and 65 females; mean age of 61.1 ± 9.2) who visited Kurume University Hospital for a riskscreening test or treatment for cardiovascular disease to look at the relationship between DPP-4 and PEDF a priori, although a part of subjects were enrolled in our previous study [5]. We excluded any patients with inflammatory, neoplastic disorders, and those who had a recent (b3 months) acute coronary syndrome, stroke and any acute infection.…”

“…Since circulating AGE levels are independently correlated with serum DPP-4 levels [5], cumulative hyperglycemia and resultant AGE formation may impair the effects of incretins via elevation of circulating DPP-4 levels, further deteriorating glycemic control and progressing vascular damage in diabetes.…”

“…Further, we have recently found that AGEs stimulate the proteolytic cleavage of dipeptidyl peptidase-4 (DPP-4) from plasma membranes on both proximal tubular cells and endothelial cells, major cell types that expressed DPP-4 [5][6][7].…”