scholarly journals Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 5603
Author(s):  
Anna Litwiniuk ◽  
Wojciech Bik ◽  
Małgorzata Kalisz ◽  
Agnieszka Baranowska-Bik
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Chronic Inflammation ◽  
Amyloid Β ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Neurodegenerative Dementia

Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid β (Aβ) aggregate formation. AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Adiposity is associated with the pro-inflammatory phenotype. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. NLRP3/IL-1β signaling could underlie the association between adiposity and cognitive impairment in humans. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD.

scholarly journals Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

scholarly journals Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications

2018 ◽  
Vol 19 (11) ◽  
pp. 3306 ◽  
Author(s):  
Andrea Tumminia ◽  
Federica Vinciguerra ◽  
Miriam Parisi ◽  
Lucia Frittitta
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Cell Activation ◽  
Insulin Signalling ◽  
Amyloid Β ◽  
Neuronal Stem Cell

In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer’s disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid β accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment.

scholarly journals Pathology, Risk Factors, and Oxidative Damage Related to Type 2 Diabetes-Mediated Alzheimer’s Disease and the Rescuing Effects of the Potent Antioxidant Anthocyanin

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Muhammad Sohail Khan ◽  
Muhammad Ikram ◽  
Tae Ju Park ◽  
Myeong Ok Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Acid Oxidation ◽  
Chronic Hyperglycemia ◽  
Underlying Mechanisms

The pathology and neurodegeneration in type 2 diabetes- (T2D-) mediated Alzheimer’s disease (AD) have been reported in several studies. Despite the lack of information regarding the basic underlying mechanisms involved in the development of T2D-mediated AD, some common features of the two conditions have been reported, such as brain atrophy, reduced cerebral glucose metabolism, and insulin resistance. T2D phenotypes such as glucose dyshomeostasis, insulin resistance, impaired insulin signaling, and systemic inflammatory cytokines have been shown to be involved in the progression of AD pathology by increasing amyloid-beta accumulation, tau hyperphosphorylation, and overall neuroinflammation. Similarly, oxidative stress, mitochondrial dysfunction, and the generation of advanced glycation end products (AGEs) and their receptor (RAGE) as a result of chronic hyperglycemia may serve as critical links between diabetes and AD. The natural dietary polyflavonoid anthocyanin enhances insulin sensitivity, attenuates insulin resistance at the level of the target tissues, inhibits free fatty acid oxidation, and abrogates the release of peripheral inflammatory cytokines in obese (prediabetic) individuals, which are responsible for insulin resistance, systemic hyperglycemia, systemic inflammation, brain metabolism dyshomeostasis, amyloid-beta accumulation, and neuroinflammatory responses. In this review, we have shown that obesity may induce T2D-mediated AD and assessed the recent therapeutic advances, especially the use of anthocyanin, against T2D-mediated AD pathology. Taken together, the findings of current studies may help elucidate a new approach for the prevention and treatment of T2D-mediated AD by using the polyflavonoid anthocyanin.

Amyloid‐β and islet amyloid pathologies link Alzheimer’s disease and type 2 diabetes in a transgenic model

2017 ◽  
Vol 31 (12) ◽  
pp. 5409-5418 ◽  
Author(s):  
Nadeeja Wijesekara ◽  
Rosemary Ahrens ◽  
Miheer Sabale ◽  
Ling Wu ◽  
Kathy Ha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Islet Amyloid ◽  
Transgenic Model

scholarly journals Elevated Serum TNF-α Is Related to Obesity in Type 2 Diabetes Mellitus and Is Associated with Glycemic Control and Insulin Resistance

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Hana Alzamil
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Inflammation ◽  
Affinity Column ◽  
Diabetic Patients ◽  
Low Grade ◽  
Model Assessment

Background. Diabetes and obesity are very common associated metabolic disorders that are linked to chronic inflammation. Leptin is one of the important adipokines released from adipocytes, and its level increases with increasing body mass index (BMI). Tumor necrosis factor alpha (TNF-α) is a cytokine that is released by adipocytes and inflammatory cells in response to chronic inflammation. Type 2 diabetes mellitus (T2DM) is believed to be associated with low-grade chronic inflammation. The current study aims to investigate the involvement of leptin and TNF-α in T2DM associated with obesity. Methodology. This is a cross-sectional study involving 63 healthy volunteers and 65 patients with T2DM. Body composition was measured, and fasting venous blood samples were analyzed for blood glucose, glycosylated hemoglobin (HbA1c), basal insulin, leptin, and TNF-α. HbA1c was measured by the affinity column method. Insulin, leptin, and TNF-α immunoassays were performed by the ELISA technique. Insulin resistance and beta-cell function were assessed using the homeostasis model assessment (HOMA-IR and HOMA-B). Results. Our study showed a significantly higher level of TNF-α in T2DM patients compared to controls (7.51 ± 2.48 and 6.19 ± 3.01, respectively; p=0.008). In obese diabetic patients, the serum level of TNF-α was significantly higher in comparison with nonobese diabetic patients (p<0.018) and obese nondiabetic group (p<0.001). TNF-α correlated positively with HbA1c (r = 0.361, p=0.003) and HOMA-IR (r = 0.296, p=0.017) in patients with T2DM. Conclusion. TNF-α is associated with concurrent obesity and T2DM and correlates with HbA1c. This suggests that TNF-α needs further investigation to explore if it has a role in monitoring the effectiveness of management in individuals with obesity and T2DM.

scholarly journals Type 2 diabetes mellitus in the pathophysiology of Alzheimer's disease

2017 ◽  
Vol 11 (2) ◽  
pp. 105-113 ◽  
Author(s):  
Aparecida Marcelino de Nazareth
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Senile Plaques ◽  
Amyloid Aβ ◽  
Β Amyloid

ABSTRACT Both Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are two common forms of disease worldwide and many studies indicate that people with diabetes, especially DM, are at higher risk of developing AD. AD is characterized by progressive cognitive decline and accumulation of β-amyloid (Aβ) forming senile plaques. DM is a metabolic disorder characterized by hyperglycemia in the context of insulin resistance and relative lack of insulin. Both diseases also share common characteristics such as loss of cognitive function and inflammation. Inflammation resulting from Aβ further induces production of Aβ1-42 peptides. Inflammation due to overnutrition induces insulin resistance and consequently DM. Memory deficit and a decrease in GLUT4 and hippocampal insulin signaling have been observed in animal models of insulin resistance. The objective of this review was to show the shared characteristics of AD and DM.

scholarly journals Muscle Insulin Resistance and the Inflamed Microvasculature: Fire from Within

2019 ◽  
Vol 20 (3) ◽  
pp. 562 ◽  
Author(s):  
Jia Liu ◽  
Zhenqi Liu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Action ◽  
Microvascular Perfusion ◽  
Glucose Disposal ◽  
Inflammatory Factors ◽  
Early Event ◽  
Low Grade ◽  
Obesity And Diabetes

Insulin is a vascular hormone and regulates vascular tone and reactivity. Muscle is a major insulin target that is responsible for the majority of insulin-stimulated glucose use. Evidence confirms that muscle microvasculature is an important insulin action site and critically regulates insulin delivery to muscle and action on myocytes, thereby affecting insulin-mediated glucose disposal. Insulin via activation of its signaling cascade in the endothelial cells increases muscle microvascular perfusion, which leads to an expansion of the endothelial exchange surface area. Insulin’s microvascular actions closely couple with its metabolic actions in muscle and blockade of insulin-mediated microvascular perfusion reduces insulin-stimulated muscle glucose disposal. Type 2 diabetes is associated with chronic low-grade inflammation, which engenders both metabolic and microvascular insulin resistance through endocrine, autocrine and paracrine actions of multiple pro-inflammatory factors. Here, we review the crucial role of muscle microvasculature in the regulation of insulin action in muscle and how inflammation in the muscle microvasculature affects insulin’s microvascular actions as well as metabolic actions. We propose that microvascular insulin resistance induced by inflammation is an early event in the development of metabolic insulin resistance and eventually type 2 diabetes and its related cardiovascular complications, and thus is a potential therapeutic target for the prevention or treatment of obesity and diabetes.

Polymorphic cross-seeding amyloid assemblies of amyloid-β and human islet amyloid polypeptide

2015 ◽  
Vol 17 (35) ◽  
pp. 23245-23256 ◽  
Author(s):  
Mingzhen Zhang ◽  
Rundong Hu ◽  
Hong Chen ◽  
Yung Chang ◽  
Jie Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Β ◽  
Epidemiological Studies ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

Epidemiological studies have shown that the development of Alzheimer's disease (AD) is associated with type 2 diabetes (T2D), but it still remains unclear how AD and T2D are connected.

Sign in / Sign up

Export Citation Format

Share Document