The brain as an insulin-sensitive metabolic organ

Abstract

Background The brain was once thought of as an insulin-insensitive organ. We now know that the insulin receptor is present throughout the brain and serves important functions in whole-body metabolism and brain function. Brain insulin signaling is involved not only in brain homeostatic processes but also neuropathological processes such as cognitive decline and Alzheimer's disease. Scope of review In this review, we provide an overview of insulin signaling within the brain and the metabolic impact of brain insulin resistance and discuss Alzheimer's disease, one of the neurologic diseases most closely associated with brain insulin resistance. Major conclusions While brain insulin signaling plays only a small role in central nervous system glucose regulation, it has a significant impact on the brain's metabolic health. Normal insulin signaling is important for mitochondrial functioning and normal food intake. Brain insulin resistance contributes to obesity and may also play an important role in neurodegeneration.

A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer’s Disease, the 5XFAD Mouse

“…For 48 h, mice were analyzed for energy expenditure (EE, kcal/kg lean mass), respiratory quotient (RQ, VCO 2 /VO 2 ), and food intake using a calorimetric system (LabMaster, TSE System, Bad Homburg, Germany) as previously described [112]. This system is an open-circuit instrument that determines (1) the energy consumed by the amount of caloric intake (kilocalories) along time (hours) and normalized by the lean mass (kilograms) and (2) the ratio between the CO 2 production and O 2 consumption (VCO 2 /VO 2 ). Activity was measured by infrared system counting mice movement and rearing.…”

“…In addition to the well-known peripheral role for insulin on glucose and energy storage, insulin also regulates a series of cognitive processes such as memory formation through its effects on glial-neuronal metabolic coupling. Central insulin resistance is a common feature linked to premature aging and observed in neurological disorders, including early stages of Alzheimer's disease (AD) [2].…”

α-Lipoic Acid Strengthens the Antioxidant Barrier and Reduces Oxidative, Nitrosative, and Glycative Damage, as well as Inhibits Inflammation and Apoptosis in the Hypothalamus but Not in the Cerebral Cortex of Insulin-Resistant Rats

“…The pathogenesis of type 2 diabetes involves two primary metabolic defects: impaired insulin secretion and insulin resistance, defined as a reduction of tissue insulin sensitivity caused by a loss/downregulation of the insulin receptors (IR) or insulin receptor substrates (IRS-1 and IRS-2) [ 12 – 14 ]. For many years, the brain was thought of as an “insulin-insensitive” organ; however, recent reports indicated that insulin could cross the blood-brain barrier (BBB) produced within the brain structures such as the hypothalamus and cerebral cortex [ 15 – 17 ]. A significant role in the etiology of metabolic and neurodegenerative disorders is also attributed to oxidative and nitrosative stress [ 18 – 20 ].…”

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

“…Although studies on insulin action have traditionally focused on the peripheral tissue domain, more and more preclinical and clinical studies are being reported focusing on the effects of insulin resistance on the central nervous system [ 23 ], since an effect of insulin resistance in the brain was also observed in obese, DM, older, and dementia individuals [ 24 ]. Insulin receptors are present throughout the brain, therefore this hormone plays important roles not only in the metabolism of the whole body, but also in brain functioning, being, therefore, involved in neuropathological processes [ 25 ]. This occurs because insulin is able to cross the blood-brain barrier.…”