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Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions

Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormali...

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Detalles Bibliográficos
Autores principales: Pomytkin, Igor, Pinelis, Vsevolod
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005009/
https://www.ncbi.nlm.nih.gov/pubmed/33810179
http://dx.doi.org/10.3390/life11030262
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author Pomytkin, Igor
Pinelis, Vsevolod
author_facet Pomytkin, Igor
Pinelis, Vsevolod
author_sort Pomytkin, Igor
collection PubMed
description Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin.
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spelling pubmed-80050092021-03-29 Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions Pomytkin, Igor Pinelis, Vsevolod Life (Basel) Review Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin. MDPI 2021-03-22 /pmc/articles/PMC8005009/ /pubmed/33810179 http://dx.doi.org/10.3390/life11030262 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Review
Pomytkin, Igor
Pinelis, Vsevolod
Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
title Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
title_full Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
title_fullStr Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
title_full_unstemmed Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
title_short Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
title_sort brain insulin resistance: focus on insulin receptor-mitochondria interactions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005009/
https://www.ncbi.nlm.nih.gov/pubmed/33810179
http://dx.doi.org/10.3390/life11030262
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