Abstract
Insulin plays a range of roles as an anabolic hormone in peripheral tissues. It regulates glucose metabolism, stimulates glucose transport into cells and suppresses hepatic glucose production. Insulin influences cell growth, differentiation and protein synthesis, and inhibits catabolic processes such as glycolysis, lipolysis and proteolysis. Insulin and insulin-like growth factor-1 receptors are expressed on all cell types in the central nervous system. Widespread distribution in the brain confirms that insulin signaling plays important and diverse roles in this organ. Insulin is known to regulate glucose metabolism, support cognition, enhance the outgrowth of neurons, modulate the release and uptake of catecholamine, and regulate the expression and localization of gamma-aminobutyric acid (GABA). Insulin is also able to freely cross the blood–brain barrier from the circulation. In addition, changes in insulin signaling, caused inter alia insulin resistance, may accelerate brain aging, and affect plasticity and possibly neurodegeneration. There are two significant insulin signal transduction pathways: the PBK/AKT pathway which is responsible for metabolic effects, and the MAPK pathway which influences cell growth, survival and gene expression. The aim of this study is to describe the role played by insulin in the CNS, in both healthy people and those with pathologies such as insulin resistance and Alzheimer’s disease.
Highlights
Rostagno, Agnieszka Baranowska-BikHuman insulin is a 51-amino acid peptide hormone consisting of two chains, synthesized in the β-cells of the islets of Langerhans in the pancreas
The activation of the insulin–insulin receptor (IR)–IRS–PI3K–AKT pathway regulates the phosphorylation of many intracellular proteins, such as serine/threonine-protein kinase mTOR, glycogen synthase kinase 3β (GSK3β), cAMP-responsive element-binding protein (CREB), filamin A and nitric oxide synthetases
Parkinson’s disease and dementia with Lewy bodies (DLB) frequently overlap with Alzheimer’s disease, which is linked to brain impairments in insulin, insulin-like growth factor, and neurotrophin signaling
Summary
Human insulin is a 51-amino acid peptide hormone consisting of two chains, synthesized in the β-cells of the islets of Langerhans in the pancreas. It promotes the uptake of fatty acids and amino acids and enables energy storage It inhibits processes, such as glycolysis, lipolysis and proteolysis. Insulin binds to the insulin receptor (IR) to form an insulin–insulin receptor complex, which is transported by transcytosis through the brain to the endothelial cells. This transport can be modulated by several factors, such as a high-fat diet, astrocyte stimulation [4], obesity, inflammation, diabetes mellitus, and circulating triglyceride levand Arkadiusz Orzechowski. It may be produced by choroid plexus, but its release is modulated, not by glucose, but by serotonin
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