ArticlePloS one2015
Endoplasmic reticulum stress impairs insulin receptor signaling in the brains of obese rats.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- 1,25-dihydroxyvitamin DNutrition research and practice · 2024Article
- Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated.Nutrients · 2023Review
- Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer's Disease.TouchREVIEWS in endocrinology · 2023Review
- Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors.Nutrients · 2022Review
- Behavioral and Molecular Effects of Thapsigargin-Induced Brain ER- Stress: Encompassing Inflammation, MAPK, and Insulin Signaling Pathway.Life (Basel, Switzerland) · 2022Article
- Impaired insulin signalling and allostatic load in Alzheimer disease.Nature reviews. Neuroscience · 2022Review
- The Role of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) in Diabetes-Related Neurodegenerative Diseases.Drug design, development and therapy · 2022Review
- Lipotoxicity suppresses the synthesis of growth hormone in pituitary somatotrophs via endoplasmic reticulum stress.Journal of cellular and molecular medicine · 2021Article
- Potential Roles of Endoplasmic Reticulum Stress and Cellular Proteins Implicated in Diabesity.Oxidative medicine and cellular longevity · 2021Review
- Tauroursodeoxycholic Acid Attenuates Diet-Induced and Age-Related Peripheral Endoplasmic Reticulum Stress and Cerebral Amyloid Pathology in a Mouse Model of Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2021Article
- Endoplasmic Reticulum Stress and miRNA Impairment in Aging and Age-Related Diseases.Frontiers in aging · 2021Review
- Regulation of autophagy by canonical and non-canonical ER stress responses.Seminars in cancer biology · 2020Review
- Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain.Antioxidants (Basel, Switzerland) · 2020Review
- Article
- Zonisamide Ameliorates Cognitive Impairment by Inhibiting ER Stress in a Mouse Model of Type 2 Diabetes Mellitus.Frontiers in aging neuroscience · 2020Article
- Article
- Involvement of insulin receptor substrates in cognitive impairment and Alzheimer's disease.Neural regeneration research · 2019Review
- Endoplasmic Reticulum Stress Activates Unfolded Protein Response Signaling and Mediates Inflammation, Obesity, and Cardiac Dysfunction: Therapeutic and Molecular Approach.Frontiers in pharmacology · 2019Review
- Brain GLP-1/IGF-1 Signaling and Autophagy Mediate Exendin-4 Protection Against Apoptosis in Type 2 Diabetic Rats.Molecular neurobiology · 2018Article
- The role of endoplasmic reticulum stress in hippocampal insulin resistance.Experimental neurology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The incidence of obesity is increasing worldwide. It was reported that endoplasmic reticulum stress (ERS) could inhibit insulin receptor signaling by activating c-Jun N-terminal kinase (JNK) in the liver. However, the relationship between ERS and insulin receptor signaling in the brain during obesity remains unclear. The aim of the current study was to assess whether ERS alters insulin receptor signaling through the hyper-activation of JNK in the hippocampus and frontal cortex in the brains of obese rats. Obesity was induced using a high fat diet (HFD). The Morris water maze test was then performed to evaluate decreases in cognitive function, and western blot was used to verify whether abnormal insulin receptor signaling was induced by ERS in HFD rats exhibiting cognitive decline. In addition, to determine whether ERS activated JNK and consequently impaired insulin receptor signaling, SH-SY5Y cells were treated with the JNK inhibitor, SP600125, followed by tunicamycin or thapsigargin, and primary rat hippocampal and cortical neurons were transfected with siRNA against IRE1α and JNK. We found that the expression of phosphorylation of PKR-like kinase (PERK), phosphorylation of α subunit of translation initiation factor 2 (eIF2α), and phosphorylation of inositol-requiring kinase-1α (IRE-1α) were increased in the brains of rats with HFD when compared with control rats. The level of serine phosphorylation of insulin receptor substrate-1 (IRS-1) was also increased, while protein kinase B (PKB/Akt) was reduced. ERS was also found to inhibit insulin receptor signaling via the activation of JNK in SH-SY5Y cells, primary rat hippocampal, and cortical neurons. These results indicate that ERS was increased, thereby resulting in impaired insulin receptor signaling in the hippocampus and frontal cortex of obese rats.
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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.