scholarly journals Data-Driven Modeling of Knowledge Assemblies in Understanding Comorbidity Between Type 2 Diabetes Mellitus and Alzheimer’s Disease

2020 ◽  
Vol 78 (1) ◽  
pp. 87-95
Author(s):  
Reagon Karki ◽  
Sumit Madan ◽  
Yojana Gadiya ◽  
Daniel Domingo-Fernández ◽  
Alpha Tom Kodamullil ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Relevant Literature

Background: Recent studies have suggested comorbid association between Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) through identification of shared molecular mechanisms. However, the inference is pre-dominantly literature-based and lacks interpretation of pre-disposed genomic variants and transcriptomic measurables. Objective: In this study, we aim to identify shared genetic variants and dysregulated genes in AD and T2DM and explore their functional roles in the comorbidity between the diseases. Methods: The genetic variants for AD and T2DM were retrieved from GWAS catalog, GWAS central, dbSNP, and DisGeNet and subjected to linkage disequilibrium analysis. Next, shared variants were prioritized using RegulomeDB and Polyphen-2. Afterwards, a knowledge assembly embedding prioritized variants and their corresponding genes was created by mining relevant literature using Biological Expression Language. Finally, coherently perturbed genes from gene expression meta-analysis were mapped to the knowledge assembly to pinpoint biological entities and processes and depict a mechanistic link between AD and T2DM. Results: Our analysis identified four genes (i.e., ABCG1, COMT, MMP9, and SOD2) that could have dual roles in both AD and T2DM. Using cartoon representation, we have illustrated a set of causal events surrounding these genes which are associated to biological processes such as oxidative stress, insulin resistance, apoptosis and cognition. Conclusion: Our approach of using data as the driving force for unraveling disease etiologies eliminates literature bias and enables identification of novel entities that serve as the bridge between comorbid conditions.

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 Alzheimer’s Disease and Type 2 Diabetes Mellitus: Molecular Mechanisms and Similarities

2020 ◽  
Author(s):  
Karla Isabel Lira-De León ◽  
Alma Delia Bertadillo-Jilote ◽  
David Gustavo García-Gutiérrez ◽  
Marco Antonio Meraz-Ríos
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Mechanisms

scholarly journals Effects and Underlying Mechanisms of Bioactive Compounds on Type 2 Diabetes Mellitus and Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-25 ◽  
Author(s):  
Rongzi Li ◽  
Yuxian Zhang ◽  
Suhail Rasool ◽  
Thangiah Geetha ◽  
Jeganathan Ramesh Babu
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Clinical Effects ◽  
Brain Disorder

Type 2 diabetes mellitus is a complicated metabolic disorder characterized by hyperglycemia and glucose intolerance. Alzheimer’s disease is a progressive brain disorder characterized by a chronic loss of cognitive and behavioral function. Considering the shared characteristics of both diseases, common therapeutic and preventive agents may be effective. Bioactive compounds such as polyphenols, vitamins, and carotenoids found in vegetables and fruits can have antioxidant and anti-inflammatory effects. These effects make them suitable candidates for the prevention or treatment of diabetes and Alzheimer’s disease. Increasing evidence from cell or animal models suggest that bioactive compounds may have direct effects on decreasing hyperglycemia, enhancing insulin secretion, and preventing formation of amyloid plaques. The possible underlying molecular mechanisms are described in this review. More studies are needed to establish the clinical effects of bioactive compounds.

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 Title: Biochemical linkage of type 2 diabetes mellitus and Alzheimer’s disease

2019 ◽  
Vol 0 (0) ◽  
pp. 1-14
Author(s):  
samar mahmoud ◽  
Dina Abo-El-Matty ◽  
Noha Mesbah ◽  
Eman Mehanna ◽  
Mohamed Hafez
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus

scholarly journals Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

2019 ◽  
Vol 9 (10) ◽  
pp. 262 ◽  
Author(s):  
Hayden
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Age Related ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease–dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen–nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis—vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

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