ArticleThe Journal of clinical investigation2018
Insulin regulates astrocyte gliotransmission and modulates behavior.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 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
126 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Hyperglycemia associated brain dysfunction: rodent models for studying diabetic cognitive deficits.Metabolic brain disease · 2026Review
- Astrocytic PI3Kα controls synaptic plasticity and cognitive function via serine metabolism.Nature communications · 2026Article
- Effects of Plant Polyphenols on Obesity-Induced Inflammatory Depression: A Review.International journal of molecular sciences · 2026Review
- Restoration of Neuronal Metabolism and Memory in Alzheimer's Disease by Reprogramming the Exosomal microRNA Network.Journal of molecular neuroscience : MN · 2026Review
- Prenatal metabolic adversity reprograms insulin-responsive transcription in the developing nucleus accumbens.Molecular metabolism · 2026Article
- Licochalcone a enhances cognitive resilience in APP/PS1 Mice by modulating glucose metabolism, Aβ burden, and neuroinflammation.GeroScience · 2026Article
- Impact of Semaglutide on Hippocampal Injury in a Streptozotocin-Induced Model of Alzheimer's Disease.Biomedicines · 2026Article
- Multimodal fusion of brain imaging and proteomics reveals a brain-body pathway linking depression and metabolic dysfunction.Psychological medicine · 2026Article
- Insulin Receptor Isoform Pattern in Aged Normal and Alzheimer's Human Cortex.Journal of neurochemistry · 2026Article
- Association between the gut microbiome and plasma metabolites linked to vocalization-based temperament in Merino sheep.Microbiome · 2026Article
- Empagliflozin in the Absence of Diabetes: A Systematic Review of Its Anthropometric and Metabolic Effects in Humans and Animals.International journal of endocrinology · 2026Article
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- Insulin and IGF signaling in the brain: multilevel regulation of synaptic and network homeostasis.Frontiers in endocrinology · 2026Review
- Chronic Stress and Astrocyte Dysfunction in Depression: Molecular Mechanisms and Gene Expression Changes.Antioxidants (Basel, Switzerland) · 2025Review
- Central cytometabolic functional vascular coupling in health and disease.npj metabolic health and disease · 2025Review
- Insulin evokes release of endozepines from astrocytes of the NTS to modulate glucose metabolism in male rats.Molecular metabolism · 2025Article
- Evidence of bidirectional relationship between type 2 diabetes and depression; a Mendelian randomization study.Molecular psychiatry · 2025Article
- Preliminary study on changes in volume and functional connectivity of hippocampal subregions in patients with diabetic retinopathy.Brain imaging and behavior · 2025Article
- An interoceptive model of energy allostasis linking metabolic and mental health.Science advances · 2025Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Complications of diabetes affect tissues throughout the body, including the central nervous system. Epidemiological studies show that diabetic patients have an increased risk of depression, anxiety, age-related cognitive decline, and Alzheimer's disease. Mice lacking insulin receptor (IR) in the brain or on hypothalamic neurons display an array of metabolic abnormalities; however, the role of insulin action on astrocytes and neurobehaviors remains less well studied. Here, we demonstrate that astrocytes are a direct insulin target in the brain and that knockout of IR on astrocytes causes increased anxiety- and depressive-like behaviors in mice. This can be reproduced in part by deletion of IR on astrocytes in the nucleus accumbens. At a molecular level, loss of insulin signaling in astrocytes impaired tyrosine phosphorylation of Munc18c. This led to decreased exocytosis of ATP from astrocytes, resulting in decreased purinergic signaling on dopaminergic neurons. These reductions contributed to decreased dopamine release from brain slices. Central administration of ATP analogs could reverse depressive-like behaviors in mice with astrocyte IR knockout. Thus, astrocytic insulin signaling plays an important role in dopaminergic signaling, providing a potential mechanism by which astrocytic insulin action may contribute to increased rates of depression in people with diabetes, obesity, and other insulin-resistant states.
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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 Socratic graph.