ArticleDiabetologia2004
Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: a new insight into selective nitrergic neuropathy in diabetes.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 104 citations in OpenAlex.
- Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials.Diabetologia · 2004Trial
- Postbiotic Stool Filtrates From Patients With Type 2 Diabetes Impair Mouse Intestinal Muscle Contractility Ex Vivo and Alter Enteric Cholinergic Neuronal Activity in Vivo.Neurogastroenterology and motility · 2026Article
- Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics.International journal of molecular sciences · 2024Review
- Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments.Current issues in molecular biology · 2024Review
- Sodium-glucose co-transporter (SGLT) inhibitor restores lost axonal varicosities of the myenteric plexus in a mouse model of high-fat diet-induced obesity.Scientific reports · 2020Article
- Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System.International journal of molecular sciences · 2020Article
- Undiagnosed prediabetes status is associated with a reduced effectiveness of phosphodiesterase type 5 inhibitors in men with erectile dysfunction.International journal of impotence research · 2020Article
- Glycolaldehyde induces sensory neuron death through activation of the c-Jun N-terminal kinase and p-38 MAP kinase pathways.Histochemistry and cell biology · 2020Article
- Nitrergic Enteric Neurons in Health and Disease-Focus on Animal Models.International journal of molecular sciences · 2019Review
- Anti-Inflammatory Effect of an Apigenin-Maillard Reaction Product in Macrophages and Macrophage-Endothelial Cocultures.Oxidative medicine and cellular longevity · 2019Article
- Prediabetes in Colombia: Expert Consensus.Colombia medica (Cali, Colombia) · 2017Review
- Longitudinal Patterns of Occurrence and Remission of Erectile Dysfunction in Men With Type 1 Diabetes.The journal of sexual medicine · 2017Article
- Quercetin Isolated fromJournal of diabetes research · 2016Article
- Gut region-dependent alterations of nitrergic myenteric neurons after chronic alcohol consumption.World journal of gastrointestinal pathophysiology · 2015Article
- Prolonged high fat diet ingestion, obesity, and type 2 diabetes symptoms correlate with phenotypic plasticity in myenteric neurons and nerve damage in the mouse duodenum.Cell and tissue research · 2015Article
- Differences Between Tg2576 and Wild Type Mice in the NMDA Receptor-Nitric Oxide Pathway After Prolonged Application of a Diet High in Advanced Glycation End Products.Neurochemical research · 2015Article
- Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats.World journal of diabetes · 2015Article
- Is the present cut-point to define type 2 diabetes appropriate in Latin-Americans?World journal of diabetes · 2014Review
- Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in diabetic rats: a role for neuronal ROCK.The journal of sexual medicine · 2014Article
- Diabetic gastrointestinal motility disorders and the role of enteric nervous system: current status and future directions.Neurogastroenterology and motility · 2014Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisWe have previously shown that in diabetes nitrergic neurones innervating the urogenital and gastrointestinal organs undergo a selective degenerative process. This comprises an initial insulin-reversible decrease in neuronal nitric oxide synthase (nNOS) in the axons, followed by apoptosis of the nitrergic neurones, a process that is not reversible by insulin. Since apoptosis was independent of serum glucose concentrations, and advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of diabetic complications, we have now measured AGEs in the serum and penis, pyloric sphincter and pelvic ganglia of diabetic animals at different times after streptozotocin treatment. Furthermore, we have studied their effect in vitro on human neuroblastoma (SH-SY5Y) cells in the presence or absence of nNOS expression.
methodsSerum AGEs were measured using fluorometry and ELISA. Accumulation of AGEs in the tissues was evaluated with immunohistochemistry. The viability, apoptosis and oxidative stress in SH-SY5Y cells were measured upon exposure to AGEs or high concentrations of glucose.
resultsAGEs increased gradually in the serum and tissues of streptozotocin-induced diabetic rats; this process was not affected by delayed insulin treatment. In SH-SY5Y cells, AGEs, but not high glucose concentrations, increased the reactive oxygen species and caspase-3-dependent apoptosis in a synergistic fashion with endogenous nitric oxide (NO). Apoptosis was prevented by treatment with a NOS inhibitor, a pan-caspase inhibitor, a soluble receptor of AGEs or an anti-oxidant, but not an inhibitor of soluble guanylate cyclase. CONCLUSIONS/
interpretationThe synergistic actions of NO and AGEs account for the irreversible nitrergic degeneration in diabetes.
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