ArticleBMC endocrine disorders2010
Early limited nitrosamine exposures exacerbate high fat diet-mediated type 2 diabetes and neurodegeneration.
Article in BMC endocrine disorders, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Insulin-like growth factor 1 associated research in Alzheimer's disease: an exploratory trends analysis.Frontiers in neurologyPooled it
- Associations between preservative food additives and type 2 diabetes incidence in the NutriNet-Santé prospective cohort.Nature communications · 2026Article
- Are all ultra-processed foods created equal? Relevance of food processing and nutritional quality.European journal of epidemiology · 2025Article
- Review
- Diethyl nitrosamine-induces neurobehavioral deficit, oxido-nitrosative stress in rats' brain: a neuroprotective role of diphenyl diselenide.BMC neuroscience · 2024Article
- Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer's Disease (Type 3 Diabetes).Journal of Alzheimer's disease : JAD · 2023Review
- Dietary exposure to nitrites and nitrates in association with type 2 diabetes risk: Results from the NutriNet-Santé population-based cohort study.PLoS medicine · 2023Observational
- Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling.Journal of personalized medicine · 2022Article
- The Full Spectrum of Alzheimer's Disease Is Rooted in Metabolic Derangements That Drive Type 3 Diabetes.Advances in experimental medicine and biology · 2019Review
- Discovery of High Affinity Receptors for Dityrosine through Inverse Virtual Screening and Docking and Molecular Dynamics.International journal of molecular sciences · 2018Article
- The 20-Year Voyage Aboard the Journal of Alzheimer's Disease: Docking at 'Type 3 Diabetes', Environmental/Exposure Factors, Pathogenic Mechanisms, and Potential Treatments.Journal of Alzheimer's disease : JAD · 2018Review
- Brain metabolic and functional alterations in a liver-specific PTEN knockout mouse model.PloS one · 2018Article
- Therapeutic activity of sour orange albedo extract and abundant flavanones loaded silica nanoparticles against acrylamide-induced hepatotoxicity.Toxicology reports · 2018Article
- Maternal Dietary Patterns and Gestational Diabetes Risk: A Case-Control Study.Journal of diabetes research · 2017Article
- Long-Term Stability of Volatile Nitrosamines in Human Urine.Journal of analytical toxicology · 2016Article
- Tobacco Nitrosamine Exposures Contribute to Fetal Alcohol Spectrum Disorder Associated Cerebellar Dysgenesis.International journal of biology · 2016Article
- The Rationale for Insulin Therapy in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2016Review
- Tobacco Smoke-Induced Hepatic Injury with Steatosis, Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling.Journal of clinical & experimental pathology · 2016Article
- Potential Co-Factor Role of Tobacco Specific Nitrosamine Exposures in the Pathogenesis of Fetal Alcohol Spectrum Disorder.Gynecology and obstetrics research : open journal · 2016Article
- A New Automated Method and Sample Data Flow for Analysis of Volatile Nitrosamines in Human Urine.American journal of analytical chemistry · 2016Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundType 2 diabetes mellitus (T2DM) and several types of neurodegeneration, including Alzheimer's, are linked to insulin-resistance, and chronic high dietary fat intake causes T2DM with mild neurodegeneration. Intra-cerebral Streptozotocin, a nitrosamine-related compound, causes neurodegeneration, whereas peripheral treatment causes DM. HYPOTHESIS: Limited early exposures to nitrosamines that are widely present in the environment, enhance the deleterious effects of high fat intake in promoting T2DM and neurodegeneration.
methodsLong Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. injection, and upon weaning, they were fed with high fat (60%; HFD) or low fat (5%; LFD) chow for 8 weeks. Cerebella were harvested to assess gene expression, and insulin and insulin-like growth factor (IGF) deficiency and resistance in the context of neurodegeneration.
resultsHFD +/- NDEA caused T2DM, neurodegeneration with impairments in brain insulin, insulin receptor, IGF-2 receptor, or insulin receptor substrate gene expression, and reduced expression of tau and choline acetyltransferase (ChAT), which are regulated by insulin and IGF-1. In addition, increased levels of 4-hydroxynonenal and nitrotyrosine were measured in cerebella of HFD +/- NDEA treated rats, and overall, NDEA+HFD treatment reduced brain levels of Tau, phospho-GSK-3beta (reflecting increased GSK-3beta activity), glial fibrillary acidic protein, and ChAT to greater degrees than either treatment alone. Finally, pro-ceramide genes, examined because ceramides cause insulin resistance, oxidative stress, and neurodegeneration, were significantly up-regulated by HFD and/or NDEA exposure, but the highest levels were generally present in brains of HFD+NDEA treated rats.
conclusionsEarly limited exposure to nitrosamines exacerbates the adverse effects of later chronic high dietary fat intake in promoting T2DM and neurodegeneration. The mechanism involves increased generation of ceramides and probably other toxic lipids in brain.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.