scholarly journals Sweet Bones: The Pathogenesis of Bone Alteration in Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Mohammed Al-Hariri
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Osteoblast Activity ◽  
Glycation End Products ◽  
End Products ◽  
The Status ◽  
Osteoid Surface ◽  
And Oxidative Stress

Diabetic patients have increased fracture risk. The pathogenesis underlying the status of bone alterations in diabetes mellitus is not completely understood but is multifactorial. The major deficits appear to be related to a deficit in mineralized surface area, a decrement in the rate of mineral apposition, deceased osteoid surface, depressed osteoblast activity, and decreased numbers of osteoclasts due to abnormal insulin signaling pathway. Other prominent features of diabetes mellitus are an increased urinary excretion of calcium and magnesium, accumulation of advanced glycation end products, and oxidative stress leading to sweet bones (altered bone’s strength, metabolism, and structure). Every diabetic patient should be assessed for risk factors for fractures and osteoporosis. The pathogenesis of the bone alterations in diabetes mellitus as well as their molecular mechanisms needs further study.

Glycation End-Products and their Receptors: Pathophysiology and Therapeutic Targeting in Diabetes Mellitus

2021 ◽  
Vol 1 ◽  
pp. 19-35
Author(s):  
Hussein Saad Alzadi ◽  
Naza Mohammed Ali Mahmood
Keyword(s):  
Diabetes Mellitus ◽  
Signaling Pathway ◽  
Cellular Metabolism ◽  
Fragility Fractures ◽  
Clinical Results ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Diabetes mellitus (DM) compromises cell metabolism and function in many organs, resulting in increased risks of complications in many organs such as kidney, nervous system, eye, and fragility fractures. Advanced glycation end products (AGEs) are chemical moieties produced during long-term hyperglycemia; they interact with the specific receptors for AGEs (RAGEs) and make a meaningful contribution to cellular metabolism and/or alteration of their functions. Searches in PubMed using the keywords "advanced glycation end product "RAGE", "sRAGE", "DM", and "complications” were made to reveal some of the clinical outcomes of DM in cellular metabolism and organ function through the AGE-RAGE signaling pathway. All published experimental and clinical studies were included in tables. The AGE-RAGE signaling is involved in diabetic complications such as nephropathy, neuropathy, retinopathy, and osteopathy. Some clinical results in diabetic patients could be potentially attributed to AGE-RAGE signaling consequences. However, the AGE-RAGE signaling pathway has some helpful roles in many tissues, including an increase in osteogenic function. Soluble RAGE (sRAGE), as a ligand decoy, may increase in either condition of RAGE production or destruction, and then it cannot always reflect the AGE-RAGE signaling. Although various medicines are capable to target the AGE-RAGE axis. They can also limit the associated damaging consequences. Recombinant sRAGE can block the AGE-RAGE signaling pathway; however, it is associated with some limitations such as accessibility to AGEs, increase in other RAGE ligands, and a long half-life (24 hours). It is associated with losing the beneficial effect of AGE/RAGE. As a result, sRAGE is not a helpful marker to assess the activity of the RAGE signaling pathway. The recombinant sRAGE cannot be translated into clinical practice due to its limitations.

scholarly journals Advanced Glycation end product profile of Diabetic and Non-Diabetic patients with cataract

2021 ◽  
pp. 14-20
Author(s):  
Emma-Okon B.O ◽  
Onakpoya O.H ◽  
Kolawole B.A ◽  
Owolabi F.A ◽  
Akinde M.O ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Peroxidation ◽  
Advanced Glycation End Products ◽  
Fasting Blood Glucose ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Reaction Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

The study determined the levels of advanced glycation end-products (AGEs) and malondialdehyde (MDA) in Nigerian cataract patients with and without diabetes mellitus, those with DM but no cataract as well as apparently healthy controls with a view to further elucidating putative pathophysiologic mechanisms for the occurrence of cataracts among our diabetic population. Participants comprised of 30 diabetic patients with operable cataract, 30 non-diabetic patients with operable cataract, 30 diabetic patients without cataract and 17 healthy controls all matched for age and sex, Glycated Haemoglobin levels in whole blood samples were determined using an affinity assay while fasting blood glucose was estimated by the glucose oxidase reaction. AGE was measured using a competitive ELISA kit while the level of lipid peroxidation in plasma was determined by measuring the reaction products between malondialdehyde and thiobarbituric acid. Statistical analysis was carried out using SPSS software (version 23). P<0.05 was taken as significant. The age range of participants was 52-90 years with a mean of 67.2±0.8. Mean levels of AGE were comparable in patients who had diabetes and cataract, those with cataract but no diabetes and those with Diabetes but no cataracts while healthy controls of similar age group had significantly lower levels. Patients with diabetes mellitus and cataract had significantly higher levels of MDA than those with diabetes only. There was positive, significant correlation between AGE and fasting glucose levels. No significant differences existed between AGE and MDA levels in male and female respondents. We conclude that AGE may serve as a useful index of pathologic conditions, including cataract and diabetes. Keywords: Advanced Glycation End-Products; Cataract; Diabetes; Lipid Peroxidation

scholarly journals Hydroxytyrosol Selectively Affects Non-Enzymatic Glycation in Human Insulin and Protects by AGEs Cytotoxicity

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1127
Author(s):  
Ivana Sirangelo ◽  
Margherita Borriello ◽  
Maria Liccardo ◽  
Marika Scafuro ◽  
Paola Russo ◽  
...  
Keyword(s):  
Human Insulin ◽  
Neurodegenerative Disorders ◽  
Cell Biology ◽  
Protein Glycation ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

Hydroxytyrosol (HT), the major phenolic compound in olive oil, is attracting increasing interest for its beneficial properties including a notable antioxidant and anti-inflammatory power. In this study, using a combination of biophysical and cell biology techniques, we have tested the role of HT in the formation of advanced glycation end-products (AGEs). AGEs have a key role in clinical sciences as they have been associated to diabetes, neurodegenerative and cardiovascular diseases. In addition, as the incidence of Alzheimer’s disease (AD) is strongly increased in diabetic patients, AGE formation is supposed to be involved in the development of the pathological hallmarks of AD. Our data show that HT selectively inhibits protein glycation reaction in human insulin, and it is able to counteract the AGE-induced cytotoxicity in human neurotypical cells by acting on SIRT1 level and oxidative stress, as well as on inflammatory response. This study identifies new beneficial properties for HT and suggests it might be a promising molecule in protecting against the AGE-induced toxicity, a key mechanism underlying the development and progression of neurodegenerative disorders.

scholarly journals Serum Fluorescence of Advanced Glycation End Products: A Potential Screening Tool to Distinguish Between Diabetic Patients with and without Microvascular Complications

2020 ◽  
Author(s):  
Sadaf Ali ◽  
Nivedita L Rao
Keyword(s):  
Diabetes Mellitus ◽  
Screening Tool ◽  
Microvascular Complications ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Type 2 Diabetic Patients ◽  
Glycation End Products ◽  
End Products ◽  
Type 2 Diabetic

Introduction: Enhanced formation and accumulation of Fluorescent Advanced Glycation End products (F-AGEs) in diabetes mellitus have been linked to increased risk of developing the associated vascular complications. Aim: To evaluate the potential of serum fluorescence levels of F-AGEs as screening tools to distinguish between type 2 diabetic patients with and without microvascular complications such as retinopathy, neuropathy. Materials and Methods: This cross-sectional study was conducted between June 2016 and June 2017, included 95 type 2 diabetic patients with more than 1 year of diabetes duration. Fasting blood glucose, glycated haemoglobin and total protein levels were estimated by automated methods. Serum F-AGEs were estimated by using a simple spectrofluorometric method. Microvascular complications due to diabetes mellitus were studied in each patient from medical records data on fundus examination for retinopathy and touch, vibration sensation detection for neuropathy. Diabetic patients were categorised into two groups as those without microvascular complications and those with microvascular complications-retinopathy and neuropathy. Statistical tests used for comparisons between groups were chi-square test for gender distribution, independent t-test for other parameters and Pearson’s correlations. The p-value <0.05 indicated significant difference between variables. Results: Mean age of the population was 55.1±5.3 years. Diabetic patients with microvascular complications (n=26) in the form of retinopathy, neuropathy had significantly higher levels of serum F-AGEs with mean 7.4±1.8 AU/g protein compared with diabetic patients without complications with mean value 1.5±0.7 AU/g protein (p<0.01). Conclusion: Two categories of serum fluorescent AGE values, without overlap, could be distinguished between diabetic patients with and without complications. Measurement of serum F-AGEs products has the potential to emerge as a simple, valuable screening tool to distinguish between diabetic patients with and without microvascular complications.

scholarly journals Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus

Biomolecules ◽  
2015 ◽  
Vol 5 (1) ◽  
pp. 194-222 ◽  
Author(s):  
Kerstin Nowotny ◽  
Tobias Jung ◽  
Annika Höhn ◽  
Daniela Weber ◽  
Tilman Grune
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

scholarly journals Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 876
Author(s):  
Sara Chiappalupi ◽  
Laura Salvadori ◽  
Rosario Donato ◽  
Francesca Riuzzi ◽  
Guglielmo Sorci
Keyword(s):  
Gene Polymorphisms ◽  
Renin Angiotensin System ◽  
Molecular Target ◽  
Advanced Glycation ◽  
Angiotensin System ◽  
Major Player ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

The receptor for advanced glycation-end products (RAGE) is a multiligand receptor with a role in inflammatory and pulmonary pathologies. Hyperactivation of RAGE by its ligands has been reported to sustain inflammation and oxidative stress in common comorbidities of severe COVID-19. RAGE is essential to the deleterious effects of the renin–angiotensin system (RAS), which participates in infection and multiorgan injury in COVID-19 patients. Thus, RAGE might be a major player in severe COVID-19, and appears to be a useful therapeutic molecular target in infections by SARS-CoV-2. The role of RAGE gene polymorphisms in predisposing patients to severe COVID-19 is discussed. 

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