Review
Version 1
Preserved in Portico This version is not peer-reviewed
Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions
Version 1
: Received: 12 March 2021 / Approved: 15 March 2021 / Online: 15 March 2021 (11:46:08 CET)
A peer-reviewed article of this Preprint also exists.
Pomytkin, I.; Pinelis, V. Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions. Life 2021, 11, 262. Pomytkin, I.; Pinelis, V. Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions. Life 2021, 11, 262.
Abstract
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.
Keywords
insulin; insulin receptor; brain insulin resistance; mitochondria; brain; neuron; H2O2; glutamate excitotoxicity.
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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