Advanced Glycation End Product Inhibitor Pyridoxamine Attenuates IVD Degeneration in Type 2 Diabetic Rats

Type 2 diabetes mellitus (T2DM) is associated with advanced glycation end product (AGE) enrichment and considered a risk factor for intervertebral disc (IVD) degeneration. We hypothesized that systemic AGE inhibition, achieved using pyridoxamine (PM), attenuates IVD degeneration in T2DM rats. To induce IVD degeneration, lumbar disc injury or sham surgery was performed on Zucker Diabetic Sprague Dawley (ZDSD) or control Sprague Dawley (SD) rats. Post-surgery, IVD-injured ZDSD rats received daily PM dissolved in drinking water or water only. The resulting groups were SD uninjured, SD injured, ZDSD uninjured, ZDSD injured, and ZDSD injured + PM. Levels of blood glycation and disc degeneration were investigated. At week 8 post-surgery, glycated serum protein (GSP) levels were increased in ZDSDs compared to SDs. PM treatment attenuated this increase. Micro-MRI analysis demonstrated IVD dehydration in injured versus uninjured SDs and ZDSDs. In the ZDSD injured + PM group, IVD dehydration was diminished compared to ZDSD injured. AGE levels were decreased and aggrecan levels increased in ZDSD injured + PM versus ZDSD injured rats. Histological and immunohistochemical analyses further supported the beneficial effect of PM. In summary, PM attenuated GSP levels and IVD degeneration processes in ZDSD rats, demonstrating its potential to attenuate IVD degeneration in addition to managing glycemia in T2DM.

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Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

World Journal of Diabetes ◽

10.4239/wjd.v6.i4.662 ◽

2015 ◽

Vol 6 (4) ◽

pp. 662 ◽

Cited By ~ 10

Author(s):

Peng-Min Chen ◽

Hans Gregersen ◽

Jing-Bo Zhao

Keyword(s):

Gastrointestinal Tract ◽

Diabetic Rats ◽

Advanced Glycation ◽

Advanced Glycation End Product ◽

Product Expression ◽

Type 2 Diabetic

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Advanced glycation end product levels were correlated with inflammation and carotid atherosclerosis in type 2 diabetes patients

Open Life Sciences ◽

10.1515/biol-2020-0042 ◽

2020 ◽

Vol 15 (1) ◽

pp. 364-372 ◽

Cited By ~ 1

Author(s):

Jie Li ◽

Haiyan Shangguan ◽

Xiaoqian Chen ◽

Xiao Ye ◽

Bin Zhong ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Color Doppler ◽

Enzyme Linked Immunosorbent Assay ◽

Advanced Glycation ◽

Advanced Glycation End Product ◽

Inflammatory Status ◽

Tnf Α ◽

Ifn Γ

AbstractDiabetes mellitus with atherosclerosis (AS) adds to the social burden. This study aimed to investigate whether advanced glycation end product (AGE) levels were correlated with inflammation and carotid AS (CAS) in type 2 diabetes mellitus (T2DM) patients. A total of 50 elderly T2DM patients and 50 age-matched senior healthy subjects were recruited in this study. T2DM patients were classified into two groups based on the intima–media thickness (IMT) of the carotid artery from color Doppler ultrasonography. Patients with IMT > 1 mm were classified into the T2DM + CAS group (n = 28), and patients with IMT < 1 mm were assigned as the T2DM + non-atherosclerosis (NAS) group (n = 22). The plasma levels of AGEs, receptor for AGE (RAGE), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) of all subjects were measured by enzyme-linked immunosorbent assay. The T-lymphocyte subsets were analyzed by a flow detector. T2DM + CAS patients showed significantly higher concentrations of AGEs, RAGE, TNF-α, and IFN-γ in the peripheral blood. The highest levels of CD4+ T cells were observed in the T2DM + CAS group. The AGE level was positively correlated with the concentrations of RAGE, TNF-α, IFN-γ, and CD4+. In summary, the results showed that the levels of AGEs may be correlated with the inflammatory status in T2DM patients with CAS.

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