Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor

Ishibashi, Yuji; Matsui, Takanori; Maeda, Sayaka; Higashimoto, Yuichiro; Yamagishi, Sho‐ichi

doi:10.1186/1475-2840-12-125

Cited by 145 publications

(141 citation statements)

References 50 publications

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“…MCI risk increased across nitrotyrosine and 8-iso-PGF2a quartiles. DPP4 increases reactive oxygen species generation in endothelial cells in a dose-dependent manner (25). Consistently, our data also supported a positive relationship among nitrotyrosine, 8-iso-PGF2a, and DPP4 activity.…”

Section: Discussionsupporting

confidence: 78%

Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China

et al. 2016

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OBJECTIVEHyperglycemia, inflammation, and oxidative stress are thought to be involved in the pathogenesis of cognitive decline. Dipeptidyl peptidase-4 (DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODSWe evaluated plasma DPP4 activity, inflammatory markers, and oxidative stress parameters in a cross-sectional sample of 1,160 patients with type 2 diabetes aged 60 years or older in China. MCI was diagnosed based on criteria established by the National Institute on Aging-Alzheimer's Association workgroups RESULTSPatients in the highest quartile of DPP4 activity had higher HbA 1c , interleukin 6 (IL-6), CRP, nitrotyrosine, 8-iso-PGF2a, and lower Montreal Cognitive Assessment (MoCA) scores compared with subjects in the lowest quartile (P < 0.001). In the highest DPP4 quartile, MCI risk was higher (odds ratio 3.49; 95% CI 1.97-4.57) than in the lowest quartile after adjustment for potential confounders. The risk for MCI increased more with higher levels of DPP4 activity, IL-6, CRP, nitrotyrosine, and 8-iso-PGF2a (P < 0.05), but not with higher levels of HbA 1c . CONCLUSIONSThis study shows that increased DPP4 activities are independently associated with MCI in elderly patients with type 2 diabetes. The mechanisms might be partly explained by the effect of DPP4 on inflammation and oxidative stress. These observations raise further interest in DPP4 activity for its potential effect on these MCI-related risk factors as a biological marker or even a possible therapeutic target for MCI.Type 2 diabetes is associated with an increased risk of accelerated age-related cognitive impairment and a higher incidence of dementia (1). Dementia is generally preceded by an intermediate stage, termed mild cognitive impairment (MCI), in which patients have cognitive complaints and objective disturbances on cognitive tests but in which their daily functioning is largely preserved (2). Although not all

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Section: Discussionsupporting

confidence: 78%

Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China

et al. 2016

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“…22 In this study, we found first that accumulation levels of AGEs, RAGE gene expression and oxidative stress markers, nitrotyrosine and 8-OHdG levels in the kidneys were increased in STZ rats compared with Control rats, all of which were significantly suppressed in DPP-4-deficient STZ rats. DPP-4 deficiency also inhibited the increase in renal ICAM-1 mRNA levels, glomerular area and albuminuria in STZ rats.…”

Section: Dpp-4 and Age-rage T Matsui Et Almentioning

confidence: 70%

“…36,37 Urinary ICAM-1/creatinine ratio in type 2 diabetic patients with microalbuminuria was much higher than those in normal controls, and intensive insulin treatment significantly reduced urinary ICAM-1 and albumin excretions. 38 Since the AGE-RAGE-induced oxidative stress generation enhances ICAM-1 expression in various types of cells, 18,20,22,39,40 our present study suggests that DPP-4 deficiency could inhibit renal damage in STZ rats by suppressing ICAM-1 expression in the kidneys partly through the blockade of the deleterious effects of AGE-RAGE system.…”

Section: Dpp-4 and Age-rage T Matsui Et Almentioning

confidence: 81%

“…22 In addition, linagliptin treatment was found to decrease renal levels of AGEs and 8-OHdG levels, suppresses RAGE and ICAM-1 gene expression in the kidneys and reduces albuminuria in STZ rats, although it did not affect blood glucose levels in the animals. 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.…”

Section: Discussionmentioning

confidence: 99%

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

Matsui

Nakashima

Nishino

et al. 2015

Laboratory Investigation

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Advanced glycation end products (AGEs) and their receptor (RAGE) have a role in diabetic nephropathy. We have recently found that linagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP-4), could inhibit renal damage in type 1 diabetic rats by suppressing the AGE-RAGE axis. However, it remains unclear whether DPP-4 deficiency could also have beneficial effects on experimental diabetic nephropathy. To address the issue, we rendered wild-type F344/NSlc and DPP-4-deficient F344/DuCrl/Crlj rats diabetic by injection of streptozotocin, and then investigated whether DPP-4 deficiency could block the activation of AGE-RAGE axis in the diabetic kidneys and resultantly ameliorate renal injury in streptozotocin-induced diabetic rats. Compared with control rats at 9 and 11 weeks old, body weight and heart rates were significantly lower, while fasting blood glucose was higher in wild-type and DPP-4-deficient diabetic rats at the same age. There was no significant difference of body weight, fasting blood glucose and lipid parameters between the two diabetic rat strains. AGEs, 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nitrotyrosine levels in the kidney, renal gene expression of RAGE and intercellular adhesion molecule-1, glomerular area, urinary excretion of 8-OHdG and albumin, and the ratio of renal to body weight were increased in wild-type diabetic rats at 9 and/or 11 weeks old compared with age-matched control rats, all of which except for urinary 8-OHdG levels at 11 weeks old were significantly suppressed in DPP-4-deficient diabetic rats. Our present study suggests that DPP-4 deficiency could exert beneficial actions on type 1 diabetic nephropathy partly by blocking the AGE-RAGE axis. DPP-4 might be a novel therapeutic target for preventing diabetic nephropathy. Sugars, including glucose and fructose, can react nonenzymatically with the amino groups of proteins, lipids and nucleic acids to form reversible Schiff bases, and then Amadori products. 1-3 These early glycation products undergo further complex reactions such as rearrangement, dehydration and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives called 'advanced glycation end products (AGEs)'. 1-3 The process of non-enzymatic glycation is also known as Maillard reaction, and formation and accumulation of AGEs in various tissues have progressed at a physiological aging and at an extremely accelerated rate under diabetes. [1][2][3] There is a growing body of evidence that AGEs and their receptor (RAGE) interaction evoke oxidative stress generation and inflammatory and fibrotic reactions, thereby causing progressive alteration in renal architecture and loss of renal function in diabetes. [4][5][6][7][8] Furthermore, RAGEoverexpressing diabetic mice have been shown to exhibit progressive glomerulosclerosis with renal dysfunction, compared with diabetic littermates lacking the RAGE transgene. 9 Diabetic homozygous RAGE null mice displayed diminished albuminuria and glomerulosclerosis and failed to develop significantly increased mesan...

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“…and/or bring about changes in antioxidant capacity. 6,7 The impaired cellular redox system is evidenced preclinically as well as clinically, to in turn activate various pathways including polyol pathway flux, AGE formation, and hexosamine pathway flux, and activation of protein kinase-C etc., mediating the development and aggravation of diabetic complications. 8 Further, various endogenous and exogenous antioxidant agents, in addition to many other phytochemicals present in food possessing antioxidant activity are found to be protective against the deleterious effects of free radical species during diabetes.…”

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confidence: 99%

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2016

IJPSR

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Evidence implicates hyperglycemia induced oxidative stress as a key factor in the pathogenesis of both microvascular and macrovascular complications in the body. Our main objective behind this study was to explore the beneficial effect of Caesalpinia bonducella seed kernel extract on Streptozotocin-induced hyperglycaemia and oxidative damage in rats. Rats were made hyperglycemic by single intravenous injection of Streptozotocin 40mg/kg of body weight. Hyperglycemic rats treated with extract in three different doses of 200, 400 and 600 mg/kg of body weight orally for 21 days shows a significant decrease in blood glucose, HbA1c, free amino groups whereas an increase in serum insulin level, liver glycogen contents with a significant improvement in glucose tolerance. Furthermore, above extract supplementation significantly decreases the pancreatic thiobarbituric acid-reactive substances levels along with an increase in superoxide dismutase, catalase and glutathione contents in pancreatic tissues in treatment groups when compared with control hyperglycemic rats. Treatment with above extract has lessened the severities of degenerative changes in pancreas and also in the liver tissues as compared to that of untreated control rat with hyperglycemia. Our results suggest that the ethanolic extract of Caesalpinia bonducella seed kernel improves the antioxidant defense under hyperglycemic condition and also exhibit strong anti-hyperglycaemic effect in dose dependent manner.

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Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor

Cited by 145 publications

References 50 publications

Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China

Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China

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

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