Insulin Resistance and Oxidative Stress in the Brain: What’s New?

Abstract

The latest studies have indicated a strong relationship between systemic insulin resistance (IR) and higher incidence of neurodegeneration, dementia, and mild cognitive impairment. Although some of these abnormalities could be explained by chronic hyperglycaemia, hyperinsulinemia, dyslipidaemia, and/or prolonged whole-body inflammation, the key role is attributed to the neuronal redox imbalance and oxidative damage. In this mini review, we provide a schematic overview of intracellular oxidative stress and mitochondrial abnormalities in the IR brain. We highlight important correlations found so far between brain oxidative stress, ceramide generation, β-amyloid accumulation, as well as neuronal apoptosis in the IR conditions.

A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

“…This leads to the formation of considerable amounts of superoxide anions that exceed the antioxidant capacity of the body [37]. However, chronic inflammation is also associated with enhanced production of ROS in obese patients [38,39]. Adipokines secreted by adipose tissue activate the transcription factor NF-κB (nuclear factor-kappa B), which enhances NADPH oxidase (NOX) activity and stimulates phagocytes.…”

“…Adipokines secreted by adipose tissue activate the transcription factor NF-κB (nuclear factor-kappa B), which enhances NADPH oxidase (NOX) activity and stimulates phagocytes. Indeed, phagocytes are a rich source of superoxide radicals that produce their large quantities during respiratory burst [39,40]. Under these conditions, the active center of SOD can be inactivated by enhanced levels of free radicals.…”

“…Indeed, by combining with a specific receptor (RAGE), AGEs increase the production of ROS (through NOX induction), but also enhance the expression of the NF-κB pathway. Under these conditions, other signal routes (MAP-kinases, NJK and p21RAS) can be activated [39,52]. It is suggested that AGEs may play a key role in the development of insulin resistance [39,52].…”

“…Under these conditions, other signal routes (MAP-kinases, NJK and p21RAS) can be activated [39,52]. It is suggested that AGEs may play a key role in the development of insulin resistance [39,52]. However, the AGE level was diminished twelve months after bariatric surgery.…”

Changes in Metabolic Syndrome Status and Risk of Dementia

“…In studying MS components, improvement of blood glucose mostly lowered the risk of dementia (aHR 1.27 in persistent MS versus 1.05 in improved group), including both AD (1.26 versus 1.04) and VD (1.35 versus 1.04). In previous studies, hyperglycemia was most consistently associated with cognitive decline compared to other MS components [11,31]. As an underlying mechanism, in insulin resistance conditions, which are closely related with hyperglycemia, increased content of oxidative modification products have been reported in serum samples.…”