Intensive insulin therapy decreases urinary MCP‐1 and ICAM‐1 excretions in incipient diabetic nephropathy

Ye, S. D.; Zheng, Min; Zhao, Lili; Qian, Ying; Yao, Xu; Ren, Aiming; Li, S. M.; Cao, Jing

doi:10.1111/j.1365-2362.2009.02203.x

Cited by 33 publications

(23 citation statements)

References 36 publications

(54 reference statements)

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“…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: 79%

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

confidence: 79%

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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“…Indeed, ICAM-1 deficiency was shown to be protective against diabetic nephropathy in obese and type 2 diabetic animals (Chow et al, 2006). In addition, urinary ICAM-1/creatinine ratio in type 2 diabetic patients with microalbuminuria was much higher than that in normal controls, and intensive insulin treatment decreased significantly urinary ICAM-1 and albumin excretions (Ye et al, 2009). Furthermore, PAI-1 is not only involved in thrombogenesis in glomerular capillary, but also plays a central role in extracellular matrix remodeling, thus contributing to the progression of diabetic nephropathy as well (Lee and Ha, 2005).…”

Section: Discussionmentioning

confidence: 96%

Glucagon-like peptide-1 inhibits angiotensin II-induced mesangial cell damage via protein kinase A

Ishibashi

Matsui

Ojima

et al. 2012

Microvascular Research

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“…Plasma MCP-1 level was associated with albumin excretion rate in patients with type 1 diabetes, a marker of early diabetic nephropathy [50]. Further, urinary MCP-1/creatinine ratios in type 2 diabetic patients with microalbuminuria were much higher than those in normal controls, and intensive insulin treatment decreased significantly the urinary MCP-1/creatinine ratios [51]. Moreover, selective targeting of MCP-1, was shown to markedly decrease albuminuria, renal injury and fibrosis in streptozotocin-induced diabetic nephropathy [52].…”

Section: Role Of Glp-1-based Therapies In Diabetic Nephropathymentioning

confidence: 94%

Pleiotropic Effects of Glucagon-like Peptide-1 (GLP-1)-Based Therapies on Vascular Complications in Diabetes

Yamagishi¹,

Matsui

2011

CPD

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Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, end-stage renal failure, acquired blindness and a variety of neuropathies, which could account for disabilities and high mortality rates in patients with diabetes. Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family. L cells in the small intestine secrete GLP-1 in response to food intake. GLP-1 not only enhances glucose-evoked insulin release from pancreatic β-cells, but also suppresses glucagon secretion from pancreatic α-cells. In addition, GLP-1 slows gastric emptying. Therefore, enhancement of GLP-1 secretion is a potential therapeutic target for the treatment of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) is a responsible enzyme that mainly degrades GLP-1, and the half-life of circulating GLP-1 is very short. Recently, DPP-4 inhibitors and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists have been developed and clinically used for the treatment of type 2 diabetes as a GLP-1-based medicine. GLP-1R is shown to exist in extra-pancreatic tissues such as vessels, kidney and heart, and could mediate the diverse biological actions of GLP-1 in a variety of tissues. So, in this paper, we review the pleiotropic effects of GLP-1-based therapies and its clinical utility in vascular complications in diabetes.

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Intensive insulin therapy decreases urinary MCP‐1 and ICAM‐1 excretions in incipient diabetic nephropathy

Abstract: Intensive insulin treatment may protect against renal injury in early DN by reducing the urinary MCP-1 and ICAM-1 excretions.

Cited by 33 publications

References 36 publications

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

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

Glucagon-like peptide-1 inhibits angiotensin II-induced mesangial cell damage via protein kinase A

Pleiotropic Effects of Glucagon-like Peptide-1 (GLP-1)-Based Therapies on Vascular Complications in Diabetes

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