ArticleDiabetologia2003
Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats.
Article in Diabetologia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 174 citations in OpenAlex.
- WNKs regulate mouse behavior and alter central nervous system glucose uptake and insulin signaling.bioRxiv : the preprint server for biology · 2025Article
- New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer's disease.Frontiers in neuroscience · 2024Review
- Brain fractalkine-CX3CR1 signalling is anti-obesity system as anorexigenic and anti-inflammatory actions in diet-induced obese mice.Scientific reports · 2022Article
- Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats.Pharmaceutics · 2021Article
- Review
- Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches.The Lancet. Neurology · 2020Review
- Antioxidative and Metabolic Effects ofNutrition and metabolic insights · 2020Article
- Green Tea Polyphenol (-)-Epigallocatechin Gallate (EGCG) Attenuates Neuroinflammation in Palmitic Acid-Stimulated BV-2 Microglia and High-Fat Diet-Induced Obese Mice.International journal of molecular sciences · 2019Article
- Sex differences in the sympathoexcitatory response to insulin in obese rats: role of neuropeptide Y.The Journal of physiology · 2019Article
- Central Administration of Insulin Combined With Resistin Reduces Renal Sympathetic Nerve Activity in Rats Fed a High Fat Diet.Frontiers in physiology · 2019Article
- Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?Frontiers in physiology · 2019Review
- Molecular Mechanisms Underlying Obesity-Induced Hypothalamic Inflammation and Insulin Resistance: Pivotal Role of Resistin/TLR4 Pathways.Frontiers in endocrinology · 2019Review
- Central and peripheral effects of physical exercise without weight reduction in obese and lean mice.Bioscience reports · 2018Article
- Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats.Molecular metabolism · 2018Article
- The PI3K/AKT pathway in obesity and type 2 diabetes.International journal of biological sciences · 2018Review
- The effects of vitamin D administration on brain inflammatory markers in high fat diet induced obese rats.BMC neuroscience · 2017Article
- iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents.Scientific reports · 2017Article
- Insulin controls food intake and energy balance via NPY neurons.Molecular metabolism · 2017Article
- Article
- The pathophysiology of defective proteostasis in the hypothalamus - from obesity to ageing.Nature reviews. Endocrinology · 2016Review
Corrections and comments
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- Expression of concern
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aim/hypothesisBy acting in the brain, insulin suppresses food intake. However, little is known with regard to insulin signalling in the hypothalamus in insulin-resistant states.
methodsWestern blotting, immunohistochemistry and polymerase chain reaction assays were combined to compare in vivo hypothalamic insulin signalling through the PI3-kinase and MAP kinase pathways between lean and obese Zucker rats.
resultsIntracerebroventricular insulin infusion reduced food intake in lean rats to a greater extent than that observed in obese rats, and pre-treatment with PI3-kinase inhibitors prevented insulin-induced anorexia. The relative abundance of IRS-2 was considerably higher than that of IRS-1 in hypothalamus of both lean and obese rats. Insulin-stimulated phosphorylation of IR, IRS-1/2, the associations of PI 3-kinase to IRS-1/2 and phosphorylation of Akt in hypothalamus were decreased in obese rats compared to lean rats. These effects seem to be mediated by increased phosphoserine content of IR, IRS-1/2 and decreased protein levels of IRS-1/2 in obese rats. In contrast, insulin stimulated the phosphorylation of MAP kinase equally in lean and obese rats. CONCLUSION/
interpretationThis study provides direct measurements of insulin signalling in hypothalamus, and documents selective resistance to insulin signalling in hypothalamus of Zucker rats. These findings provide support for the hypothesis that insulin could have anti-obesity actions mediated by the PI3-kinase pathway, and that impaired insulin signalling in hypothalamus could play a role in the development of obesity in this animal model of insulin-resistance.
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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.