Article
Food Science & Technology
Qian Wu, Yingna Feng, Yu Ouyang, Yinggang Liang, Kuoquan Zhao, Ying Wang, Qing Luo, Juan Xiao, Nianjie Feng, Mengzhou Zhou
Summary: The study demonstrated that LSOPC inhibited AGEs formation, alleviated AGEs-induced liver injury by suppressing NF-kappa B nuclear translocation and MAPK signaling pathway activation. Additionally, LSOPC also inhibited the expression of TNF-alpha and IL-6. In conclusion, LSOPC treatment potentially modulated liver injury caused by long-term dietary AGEs by suppressing the RAGE-MAPK-NF-kappa B pathways.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Aoi Takashima, Jiro Miura, Keita Sugiyama, Masato Shimizu, Misa Okada, Tomohiro Otani, Tadashi Nagashima, Tetsuya Tsuda, Tsutomu Araki
Summary: Intrapulpal calcifications can occur in the dental pulp of patients with diabetes. This study focused on the association between ectopic calcifications in the dental pulp and advanced glycation end products (AGEs) in an obese type 2 diabetic rat model. The results indicated that AGEs were strongly expressed in the dental pulp of diabetic rats, and pulpal inflammation was observed. Mechanical pressure and blood flow disorder were also factors contributing to intrapulpal calcification.
Article
Cardiac & Cardiovascular Systems
Julio A. Lamprea-Montealegre, Alice M. Arnold, Robyn L. McCLelland, Kenneth J. Mukamal, Luc Djousse, Mary L. Biggs, David S. Siscovick, Russell P. Tracy, Paul J. Beisswenger, Bruce M. Psaty, Joachim H. Ix, Jorge R. Kizer
Summary: This study found that alpha-dicarbonyl-derived AGEs are associated with CVD in an older cohort, but not in a healthier middle-aged/older cohort. The results suggest that AGEs may exert detrimental cardiovascular effects only under conditions of marked dicarbonyl and oxidative stress. Further investigation of alpha-dicarbonyl derivatives could lead to potential new strategies for CVD prevention in high-risk older populations.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Review
Urology & Nephrology
Andries Jan Smit, Saskia Corine van de Zande, Douwe Johannes Mulder
Summary: This review examines the role of skin autofluorescence (SAF) in the development of complications in diabetes and renal failure. It suggests that SAF is not only a strong predictor of type 2 diabetes development and complications, but also predicts cardiovascular disease and mortality in both individuals with diabetes and the general population.
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
(2022)
Article
Orthopedics
Zachary S. Gallate, Danielle N. D'Erminio, Philip Nasser, Damien M. Laudier, James C. Iatridis
Summary: Back and neck pain are major causes of disability, with intervertebral disc degeneration being a contributing factor. Accumulation of advanced glycation endproducts (AGEs) is associated with oxidative stress and collagen damage in the intervertebral disc. The receptors for AGEs (RAGE) and Galectin 3 (Gal3) play important roles in the response to AGEs in the intervertebral disc.
Review
Endocrinology & Metabolism
Andrea Garza-Campos, Jose Roberto Prieto-Correa, Jose Alfredo Dominguez-Rosales, Zamira Helena Hernandez-Nazara
Summary: Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases that have a high incidence globally. They have shared pathological mechanisms that can lead to the development of cancer. The review focuses on the role of the receptor for advanced glycation end products (RAGE) in obesity, T2DM, and cancer, aiming to understand the intracellular signaling mechanisms involved in cancer initiation and to develop diagnostic and therapeutic strategies to reduce the morbidity and mortality associated with these diseases.
WORLD JOURNAL OF DIABETES
(2023)
Article
Endocrinology & Metabolism
Marko Grahovac, Marko Kumric, Marino Vilovic, Dinko Martinovic, Ante Kreso, Tina Ticinovic Kurir, Josip Vrdoljak, Karlo Prizmic, Josko Bozic
Summary: The study aimed to examine the association between adherence to the Mediterranean diet (MD) and AGEs in patients with type II diabetes. Results showed that adherence to the MD was greater in patients with lower CV risk, longer disease duration, and well-controlled glycaemia.
WORLD JOURNAL OF DIABETES
(2021)
Article
Endocrinology & Metabolism
Mishaela R. Rubin, Ruban Dhaliwal
Summary: The increased risk of fractures observed in adults with type 1 diabetes (T1D) cannot be solely explained by modest decreases in areal bone mineral density (BMD). Accumulation of advanced glycation endproducts (AGEs) in bone has been suggested as a possible cause for the increased bone fragility in diabetes. Although the evidence linking AGEs and fractures in individuals with T1D is limited, recent data show that AGEs, as measured by skin intrinsic fluorescence, are a risk factor for lower BMD in T1D. Further research is needed to determine if there is a causal relationship between fractures and AGEs in T1D. If confirmed, this could lead to interventions that can reduce AGE accumulation and ultimately reduce fractures in T1D patients.
Review
Plant Sciences
Stefaniya Velichkova, Kenn Foubert, Luc Pieters
Summary: Protein glycation, a post-translational modification, is linked to glucose metabolism defects and the progression of various diseases. Research on antiglycation agents is lacking sufficient clinical data and approved drugs. Scientists are increasingly exploring natural compounds as potential inhibitors of advanced glycation endproduct formation.
Article
Physiology
Xiaoxia Huang, Bingyu Li, Jiaqing Hu, Zhuanhua Liu, Dongping Li, Zhenfeng Chen, Hang Huang, Yanjia Chen, Xiaohua Guo, Yun Cui, Qiaobing Huang
Summary: This study reveals that AGEs mediate kidney injury with characteristic patterns by binding with RAGE and inducing moesin phosphorylation. AGE-BSA stimulation in mice resulted in distinct abnormal angiogenesis, glomerular hypertrophy, mesangial expansion, glomerular atrophy, and fibrosis at different time points. Moesin phosphorylation was accompanied by these AGE-induced alterations, and moesin deficiency attenuated AGE-BSA-induced fibrosis. The phosphorylation of moesin T558 was critical in AGE-induced tube formation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Matthew Snelson, Sih Min Tan, Rachel E. Clarke, Cassandra de Pasquale, Vicki Thallas-Bonke, Tuong-Vi Nguyen, Sally A. Penfold, Brooke E. Harcourt, Karly C. Sourris, Runa S. Lindblom, Mark Ziemann, David Steer, Assam El-Osta, Michael J. Davies, Leigh Donnellan, Permal Deo, Nicole J. Kellow, Mark E. Cooper, Trent M. Woodruff, Charles R. Mackay, Josephine M. Forbes, Melinda T. Coughlan
Summary: The intake of processed foods has been associated with an increased risk of chronic kidney disease and diabetes. In rodent models, a processed diet was found to increase intestinal barrier permeability and the risk of CKD, while inhibiting the advanced glycation pathway reversed kidney injury. A high resistant starch fiber diet was shown to maintain gut barrier integrity and reduce severity of kidney injury in a mouse model of diabetes by suppressing complement activation. These findings provide insights into how processed foods contribute to chronic inflammation and disease.
Review
Biochemistry & Molecular Biology
Mariyam Khalid, Georg Petroianu, Abdu Adem
Summary: Persistent hyperglycemia in type 2 diabetes mellitus triggers a glycation reaction, resulting in the formation of AGEs. Binding of AGEs with its receptor RAGE activates various signaling pathways, leading to oxidative stress, inflammation, compromised insulin signaling, metabolic disturbances, pancreatic beta cell toxicity, and epigenetic modifications. This review summarizes the sources of AGEs, their role in metabolic dysfunction, and the AGEs/RAGE signaling cascade in type 2 diabetes mellitus and its associated complications.
Article
Biochemistry & Molecular Biology
Grit Elster Legaard, Mark Preben Printz Lyngbaek, Thomas Peter Almdal, Cody Garett Durrer, Ulrikke Nystrup, Emil List Larsen, Henrik Enghusen Poulsen, Kristian Karstoft, Bente Klarlund Pedersen, Mathias Ried-Larsen
Summary: This study aimed to investigate the effects of different volumes of exercise in adjunct to diet-induced weight loss and standard care on advanced glycation end-products (AGEs) and receptor for AGE (RAGE). The results showed that exercise in adjunct to diet-induced weight loss did not change the levels of sRAGE in persons living with well-regulated, short standing type 2 diabetes.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Nutrition & Dietetics
Marlijne C. G. de Graaf, Jean L. J. M. Scheijen, Corinne E. G. M. Spooren, Zlatan Mujagic, Marieke J. Pierik, Edith J. M. Feskens, Daniel Keszthelyi, Casper G. Schalkwijk, Daisy M. A. E. Jonkers
Summary: A Western diet high in dicarbonyls and advanced glycation endproducts (AGEs) may worsen inflammation in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This study examined the intake of dicarbonyls and AGEs in the habitual diet of IBD and IBS patients and their association with intestinal inflammation. The results showed that the absolute intake of dicarbonyls and AGEs was higher in IBD and healthy control subjects compared to IBS. However, after adjusting for energy intake, only glyoxal was lower in IBD compared to IBS and healthy controls. No significant association was found between dietary dicarbonyls and AGEs and intestinal inflammation in either patient group. The findings suggest that potential harmful effects of these compounds in the diet of Dutch patients with IBD or IBS may be counteracted by anti-inflammatory components in the food matrix.
Article
Chemistry, Physical
Vaishali Rana, Ahana Mukherjee, Yogita Basnal, Deepak Kushwaha, Jaydeep Bhattacharya, Ranjita Ghosh Moulick
Summary: The elevated blood sugar in Type II diabetes leads to the formation of Advanced Glycation Endproducts (AGEs), which cause severe pathogenic complications. Previous research has shown that AGEs generated from Hemoglobin A0 (HbA0) can synthesize gold nanoparticles (AuNPs). In this study, it was found that these AGEs can also reduce silver ions and synthesize silver nanoparticles (AgNPs) with a different plasmonic response. The research demonstrates that AGEs can be detected by deploying metal salts in solution.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Transplantation
Vicki Thallas-Bonke, Sih Min Tan, Runa S. Lindblom, Matthew Snelson, Cesare Granata, Jay Chandra Jha, Karly C. Sourris, Adrienne Laskowski, Anna Watson, Michel Tauc, Isabelle Rubera, Guoping Zheng, Ajay M. Shah, David C. H. Harris, Mahmoud H. Elbatreek, Phillip Kantharidis, Mark E. Cooper, Karin Jandeleit-Dahm, Melinda T. Coughlan
Summary: Genetic deletion of Nox4 from the proximal tubules does not influence the development of DKD, indicating that the localization of Nox4 within this kidney compartment is dispensable for the pathogenesis of chronic kidney disease in the setting of diabetes.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2021)
Article
Endocrinology & Metabolism
Matthew Snelson, Cassandra de Pasquale, Elif I. Ekinci, Melinda T. Coughlan
Summary: Changes in gut microbiota in diabetes can lead to decreased intestinal barrier function, affecting systemic inflammation and worsening microvascular diabetes complications. Prebiotics offer a dietary approach to increase beneficial short chain fatty acids produced by gut microbiota and improve intestinal permeability in diabetes.
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Food Science & Technology
Matthew Snelson, Rachel Elise Clarke, Tuong-Vi Nguyen, Sally Anne Penfold, Josephine Maree Forbes, Sih Min Tan, Melinda Therese Coughlan
Summary: The study found that long-term consumption of a high protein diet in mice can lead to kidney injury, systemic inflammation, increased gastrointestinal permeability, and alterations in the gut microbiome structure.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Article
Nutrition & Dietetics
Sih Min Tan, Runa S. J. Lindblom, Mark Ziemann, Adrienne Laskowski, Cesare Granata, Matthew Snelson, Vicki Thallas-Bonke, Assam El-Osta, Carlos D. Baeza-Garza, Stuart T. Caldwell, Richard C. Hartley, Thomas Krieg, Mark E. Cooper, Michael P. Murphy, Melinda T. Coughlan
Summary: The study investigated the use of MitoGamide to target methylglyoxal within the mitochondria for treating diabetic kidney disease (DKD), but found that it did not substantially improve the renal phenotype in an experimental model of diabetes. The findings suggest that targeting methylglyoxal within the mitochondria using MitoGamide may not be a valid therapeutic approach for DKD, and that other mitochondrial targets or processes upstream should be the focus of therapy.
Review
Endocrinology & Metabolism
Nayana Khurana, Steven James, Melinda T. Coughlan, Richard J. MacIsaac, Elif Ekinci
Summary: DKD is a growing burden, leading to the discovery of new therapies. Recent clinical trials have shown promising results with SGLT2 inhibitors, incretin-related therapies, and mineralocorticoid receptor antagonists in improving renal outcomes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Sih Min Tan, Matthew Snelson, Jakob A. Ostergaard, Melinda T. Coughlan
Summary: The pathogenesis of diabetic kidney disease (DKD) involves disrupted energy generation in the kidney, leading to inflammation and fibrosis. Recent studies have shown the involvement of the innate immune complement system, particularly Complement C5a and C3a, in regulating metabolic responses in the diabetic kidney.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Endocrinology & Metabolism
Jay C. Jha, Aozhi Dai, Jessica Garzarella, Amelia Charlton, Sofia Urner, Jakob A. Ostergaard, Jun Okabe, Chet E. Holterman, Alison Skene, David A. Power, Elif I. Ekinci, Melinda T. Coughlan, Harald H. H. W. Schmidt, Mark E. Cooper, Rhian M. Touyz, Chris R. Kennedy, Karin Jandeleit-Dahm
Summary: Excessive production of renal reactive oxygen species (ROS) plays a major role in diabetic kidney disease (DKD). This study demonstrates that NADPH oxidase 5 (NOX5) acts as a predominant pro-oxidant enzyme in DKD, independent of the previously characterized NOX4 pathway. The overexpression of NOX5 in DKD exacerbates kidney damage through enhanced ROS formation and modulation of key molecules involved in inflammation, fibrosis, and redox balance. Furthermore, the only available NOX inhibitor, GKT137831, is found to be ineffective in the presence of NOX5 expression in diabetes. These findings highlight the superior targeting potential of NOX5 as compared to other NOX isoforms like NOX4 in human DKD.
Editorial Material
Cell Biology
Matthew Snelson, Elena Rampanelli, Max Nieuwdorp, Nordin M. J. Hanssen, Melinda T. Coughlan
Summary: A recent study by Bell et al. demonstrates that dietary supplementation of modified resistant starch fibre can alter immunotolerance in individuals with type 1 diabetes.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Nutrition & Dietetics
Margaret Murray, Melinda T. Coughlan, Anne Gibbon, Vinod Kumar, Francine Z. Marques, Sophie Selby-Pham, Matthew Snelson, Kirill Tsyganov, Gary Williamson, Trent M. Woodruff, Tong Wu, Louise E. Bennett
Summary: High-heat processed foods containing resistant proteins can lead to microbial fermentation and produce metabolites that may increase the risk of chronic diseases. This study used pigs as a model and found that a resistant protein diet altered the microbiome composition and resulted in higher levels of inflammation and the potential risk of chronic kidney disease.
FRONTIERS IN NUTRITION
(2022)
Review
Endocrinology & Metabolism
Vuthi Khanijou, Neda Zafari, Melinda T. Coughlan, Richard J. MacIsaac, Elif I. Ekinci
Summary: Diabetic kidney disease is a growing concern, and there is a need to identify biomarkers that can accurately predict the risk of declining kidney function. Multiple serum and urine biomarkers of inflammation and kidney injury have shown significant association with the development and progression of diabetic kidney disease. Tumor necrosis factor receptor-1 and -2 appear to be promising markers for diabetic kidney disease, while kidney injury molecule-1, beta-2-microglobulin, and neutrophil gelatinase-associated lipocalin are potential candidates for markers of kidney injury.
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2022)
Review
Nutrition & Dietetics
Anna M. Drake, Melinda T. Coughlan, Claus T. Christophersen, Matthew Snelson
Summary: Diabetes is the leading cause of kidney disease, and resistant starch (RS) as a dietary therapy may help limit the progression of diabetic kidney disease (DKD).
Article
Multidisciplinary Sciences
Melinda T. Coughlan, Mark Ziemann, Adrienne Laskowski, Trent M. Woodruff, Sih Min Tan
Summary: Despite advances in understanding the progression of diabetic complications, diabetic kidney disease continues to be a significant health burden. In a preclinical study using diabetic mice, we found that a histone deacetylase inhibitor attenuated albuminuria and glomerulosclerosis. This inhibitor also reduced diabetes-induced upregulation of complement C5a receptors and markers of cellular senescence. Furthermore, mice lacking the C5a receptor 1 gene or treated with a C5aR1 inhibitor showed attenuated cellular senescence. These findings suggest that complement C5a mediates cellular senescence in diabetic kidney disease and complement inhibitors may serve as a novel therapeutic option.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Merlin C. Thomas, Melinda T. Coughlan, Mark E. Cooper
Summary: Recent clinical trials have shown that GLP-1RAs can have positive effects on heart and kidney outcomes in people with type 2 diabetes. This is due in part to improved glucose control and significant weight loss, but GLP-1RAs may also provide additional benefits by improving postprandial dysmetabolism.
Review
Biochemistry & Molecular Biology
Inez A. A. Trambas, Melinda T. T. Coughlan, Sih Min Tan
Summary: Diabetic kidney disease (DKD) affects a significant percentage of patients with diabetes and is the leading cause of end-stage renal disease (ESRD). The activation of the complement cascade, a component of the innate immune system, has been implicated in the development of diabetes and its complications. Inhibition of the complement system, particularly at the level of the C5a-receptor signaling axis, shows promise in reducing inflammation and fibrosis in DKD. This review discusses the role of the C5a/C5a-receptor axis in the pathogenesis of diabetes and kidney injuries, as well as the current status and mechanisms of action of complement therapeutics in development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
