ArticleProceedings of the National Academy of Sciences of the United States of America2015
Insulin resistance in brain alters dopamine turnover and causes behavioral disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 5 of them syntheses that pooled it.
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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
239 citing papers in PubMed, 5 syntheses or guidelines pooled it, 463 citations in OpenAlex.
- Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis.Scientific reports · 2025Pooled it
- Impact of diabetes mellitus type two on incidence and progression of Parkinson's disease: a systematic review of longitudinal patient cohorts.Journal of neural transmission (Vienna, Austria : 1996) · 2025Pooled it
- Neurobiological insights into the effects of ultra-processed food on lipid metabolism and associated mental health conditions: a scoping review.Frontiers in nutrition · 2025Pooled it
- Diabetes mellitus, prediabetes and the risk of Parkinson's disease: a systematic review and meta-analysis of 15 cohort studies with 29.9 million participants and 86,345 cases.European journal of epidemiology · 2023Pooled it
- Mental health and quality of life in different obesity phenotypes: a systematic review.Health and quality of life outcomes · 2022Pooled it
- Safety and tolerability of intranasal insulin in Parkinson's disease.Frontiers in neurology · 2026Trial
- Effects of weight loss intervention on anxiety, depression and quality of life in women with severe obesity and polycystic ovary syndrome.Scientific reports · 2024Trial
- Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese.JCI insight · 2022Trial
- Daytime eating prevents mood vulnerability in night work.Proceedings of the National Academy of Sciences of the United States of America · 2022Trial
- Peripheral inflammatory biomarkers define biotypes of bipolar depression.Molecular psychiatry · 2021Trial
- Novel Detection and Restorative Levodopa Treatment for Preclinical Diabetic Retinopathy.Diabetes · 2020Trial
- Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.JAMA neurology · 2019Trial
- The Interplay of Metabolic Dysfunction, Neuroinflammation, and Mitochondrial Dysfunction in Balance Impairment: Insights from Type 2 Diabetes Mellitus and Alzheimer's Disease.Molecular neurobiology · 2026Review
- Hypoadiponectinemia does not enhance anxiety-like behaviour in a lean PCOS-like mouse model.Scientific reports · 2026Article
- Chronic social defeat stress induces a hypoglycemic shift and depression-related behaviors, both prevented by antidiabetic drugs.The international journal of neuropsychopharmacology · 2026Article
- Chronic unpredictable mild Stress- induced neurobehavioral and metabolic alteration: insights into molecular mechanisms and emerging therapeutic Strategies".Psychopharmacology · 2026Review
- Blunted anticipation, but not consummation, of food rewards in depression.Cell reports. Medicine · 2026Article
- Maternal Glucose Metabolism and Emotional and Behavioral Problems in Offspring: Modification by Erythrocyte Polyunsaturated Fatty Acids.Nutrients · 2026Article
- Role of dopamine in the development of impaired counterregulation and impaired awareness of hypoglycemia.Cell reports. Medicine · 2026Article
- Association Between C-Reactive Protein-Triglyceride Glucose Index and Depressive Symptoms Among US Adults: A Nationally Representative Cross-Sectional Study From 2005 to 2023.Actas espanolas de psiquiatria · 2026Article
179 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders.
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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.