ArticleBehavioural brain research2018
Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.
Article in Behavioural brain research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Bibliometric Analysis Study on the Mechanisms of Brain Energy Metabolism Disorders in Alzheimer's Disease From 2000 to 2020.Frontiers in neurology · 2021Pooled it
- Long-acting intranasal insulin for the treatment of delirium-a randomised clinical trial.Age and ageing · 2025Trial
- Diabetes-Associated Cognitive Impairment: Pathophysiology and Emerging Therapies.Annals of clinical and translational neurology · 2026Review
- SGLT2 Inhibitors in Alzheimer's Disease: Biochemical Insights and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Central cytometabolic functional vascular coupling in health and disease.npj metabolic health and disease · 2025Review
- Fingolimod Improves Anxiety-like Behavior and Modulates Sphingosine-1-Phosphate Receptors Gene Expression in a Diabetic Mouse Model.Biomolecules · 2025Article
- Potential therapeutic benefit of exogenous ketone ester administration in delirium: a narrative review.Critical care (London, England) · 2025Review
- WNKs regulate mouse behavior and alter central nervous system glucose uptake and insulin signaling.bioRxiv : the preprint server for biology · 2025Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- A Bird's-Eye View of Glycolytic Upregulation in Activated Brain: The Major Fate of Lactate Is Release From Activated Tissue, Not Shuttling to Nearby Neurons.Journal of neurochemistry · 2025Review
- Impact of glycemic treatment and blood glucose monitoring on outcomes in patients with acute ischemic stroke without prior diabetes: a longitudinal cohort study.Diabetology & metabolic syndrome · 2024Article
- Dysregulation of energy metabolism in Alzheimer's disease.Journal of neurology · 2024Review
- Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis.Science advances · 2024Article
- Article
- Brain energy metabolism: A roadmap for future research.Journal of neurochemistry · 2024Review
- The brain insulin receptor gene network and associations with frailty index.Age and ageing · 2024Article
- Variable bioenergetic sensitivity of neurons and astrocytes to insulin and extracellular glucose.npj metabolic health and disease · 2024Article
- Insulin resistance induces earlier initiation of cognitive dysfunction mediated by cholinergic deregulation in a mouse model of Alzheimer's disease.Aging cell · 2023Article
- Why Is Iron Deficiency/Anemia Linked to Alzheimer's Disease and Its Comorbidities, and How Is It Prevented?Biomedicines · 2023Review
- Cognition from the Body-Brain Partnership: Exaptation of Memory.Annual review of neuroscience · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin.
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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.