The neuronal insulin receptor in its environment

Gralle, Matthias

doi:10.1111/jnc.13909

Cited by 64Metabolism, Diabetes, and CancerAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

The neuronal insulin receptor in its environment

Gralle, Matthias·2017·Journal of Neurochemistry

DOI 10.1111/jnc.13909

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Abstract

Insulin is known mainly for its effects in peripheral tissues, such as the liver, skeletal muscles and adipose tissue, where the activation of the insulin receptor (IR) has both short‐term and long‐term effects. Insulin and the IR are also present in the brain, and since there is evidence that neuronal insulin signaling regulates synaptic plasticity and that it is impaired in disease, this pathway might be the key to protection or reversal of symptoms, especially in Alzheimer's disease. However, there are controversies about the importance of the neuronal IR, partly because biophysical data on its activation and signaling are much less complete than for the peripheral IR. This review briefly summarizes the neuronal IR signaling in health and disease, and then focuses on known differences between the neuronal and peripheral IR with regard to alternative splicing and glycosylation, and lack of data with respect to phosphorylation and membrane subdomain localization. Particularities in the neuronal IR itself and its environment may have consequences for downstream signaling and impact synaptic plasticity. Furthermore, establishing the relative importance of insulin signaling through IR or through hybrids with its homolog, the insulin‐like growth factor 1 receptor, is crucial for evaluating the consequences of brain IR activation. An improved biophysical understanding of the neuronal IR may help predict the consequences of insulin‐targeted interventions. image

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Insulin in the brain contributes to diverse neuronal signalling mechanisms, including catecholamine release and uptake, ion channel trafficking and regulation of receptors for neurotransmitters (γ-GABA, NMDA and AMPA).
“Insulin in the brain contributes to diverse neuronal signalling mechanisms, including catecholamine release and uptake, ion channel trafficking and the regulation of receptors for neurotransmitters (ie, γ-GABA, NMDA and AMPA).117”
From Intranasal insulin (2021) · cites this paper as [117]

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Authors: Gralle, M.
Affiliations: Universidade Federal do Rio de Janeiro (BR)
Corresponding author: Gralle, Matthias
ORCID: Gralle, Matthias
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2016-12-27
Volume: 140
Issue: 3
Pages: 359-367
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/jnc.13909
OpenAlex: W2556540630
Cited by: 64
References: 115
Citations by year: 2026: 4 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 3 · 2019: 12 · 2018: 7 · 2017: 2
FWCI: 0.63
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: insulin signaling, synaptic plasticity, Alzheimer's disease, alternative splicing, receptor glycosylation, receptor phosphorylation, lipid rafts, IGF-1 receptor, brain insulin
MeSH terms: Alzheimer Disease, Animals, Brain, Humans, Insulin, Neuronal Plasticity, Neurons, Receptor, Insulin, Antigens, CD

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The neuronal insulin receptor in its environment

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