Brain insulin resistance in neurological disorders of various genesis: current state and treatment approaches

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Abstract

Nowadays, the phenomenon insulin resistance (IR) has expanded and include not only peripheral, but also central IR. However, the underlying mechanisms and physiological manifestations in the central nervous system differ from those on the periphery, and currently the concept of central IR has undergone significant changes. There are abundant evidences of the development of the nervous tissue weakened response to insulin, which directly or indirectly mediates the etiology and pathogenesis of many neurological disorders. Some molecular mechanisms underlying the decrease in the sensitivity of neurons and glial cells to insulin entering from the bloodstream to the central nervous system have been deciphered. This review is devoted to the analysis of the brain IR mechanisms in mental disorders, ischemic and traumatic brain injuries, anesthesia and postoperative stress, as well as cognitive deficits, including those associated with Alzheimer’s disease. Approaches to the diagnosis and treatment of pathological brain conditions caused by central IR are also discussed.

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About the authors

I. I. Zorina

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Author for correspondence.
Email: zorina.inna.spb@gmail.com
Russian Federation, Saint Petersburg

A. O. Shpakov

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: zorina.inna.spb@gmail.com
Russian Federation, Saint Petersburg

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2. Fig. 1. General scheme of signaling pathways activated by insulin and some effects of insulin in the central nervous system and periphery. Abbreviations: INSR/IGF1R – insulin and IGF-1 receptor; IRS – insulin receptor substrate; PI3K – phosphatidylinositol 3-kinase; AKT – serine/threonine-specific protein kinase B (AKT); mTORC1 – mammalian target of rapamycin complex 1; GLUT4 – glucose transporter type 4; GSK3β – glycogen synthase kinase-3β; FOXO1 – transcription factor FOX (forkhead box) family; PKC λ/ζ – protein kinase C λ/ζ-types; eNOS – endothelial NO synthase isoform; MAPK/ERK1/2 – mitogen-activated protein kinase signaling pathway.

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