Increasing Awareness of Type 3 Diabetes: Present and Future Implications

Background: In the United States alone, Type 2 Diabetes is the 7th leading cause of death, with Alzheimer’s Disease ahead as the 6th leading cause of mortality. While specific mechanisms have yet to be recognized by mainstream medicine, the term Type 3 Diabetes has been adopted to describe diabetes of the brain. Overarching commonalities amongst each disease include (a) oxidative stress, (b) inflammation, (c) mitochondrial dysfunction, and (d) neuroendocrine abnormalities. Collectively, these factors have been found to directly contribute to pro-death genes, impaired energy metabolism, and cerebral hypoperfusion. Yet, Type 2 Diabetes remains one of the most adjustable risk factors for the development of Alzheimer’s Disease. This dissertation explores the available literature on increasing the awareness of Type 3 Diabetes in terms of present and future implications. Methods: The review highlighted the following topics: (a) Alzheimer’s disease, (b) Types 1 and 2 diabetes, (c) insulin resistance and cognitive decline, (d) Type 3 diabetes (e) ApoE(4) genetic perturbations, (f) prevention and lifestyle support for Alzheimer’s disease, (g) prevention and lifestyle support for diabetes, (h) social and economic consequences of Alzheimer’s disease, (I) social and economic consequences of diabetes. Results: While AD is a complex disorder, there is a plethora of irrefutable research that supports viewing it as Type 3 Diabetes. Increasing patient education of Type 3 Diabetes and focusing on prevention strategies would decrease disease burden, increase quality of life and at the same time, save trillions of dollars in healthcare spending. Conclusions: Since there is no pharmaceutical cure for AD, increasing awareness of Type 3 Diabetes has the potential to provide patients with sustainable, integrative therapies, allowing them to become invested in their health choices. This will also promote individual accountability and a sense of conscientiousness in taking back one’s own health through lifestyle choices while reducing unnecessary suffering for patients, family members and society

Assembly of Connexin43 into Gap Junctions Is Regulated Differentially by E-Cadherin and N-Cadherin in Rat Liver Epithelial Cells

E-cadherin and N-cadherin affect the assembly of connexin43 into gap junctions differentially. N-cadherin disrupts assembly by triggering endocytosis of connexin43, whereas E-cadherin facilitates the assembly

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

A survey of genetic human cortical gene expression

It is widely assumed that genetic differences in gene expression underpin much of the difference among individuals and many of the quantitative traits of interest to geneticists. Despite this, there has been little work on genetic variability in human gene expression and almost none in the human brain, because tools for assessing this genetic variability have not been available. Now, with whole-genome SNP genotyping arrays and whole-transcriptome expression arrays, such experiments have become feasible. We have carried out whole-genome genotyping and expression analysis on a series of 193 neuropathologically normal human brain samples using the Affymetrix GeneChip Human Mapping 500K Array Set and Illumina HumanRefseq-8 Expression BeadChip platforms. Here we present data showing that 58% of the transcriptome is cortically expressed in at least 5% of our samples and that of these cortically expressed transcripts, 21% have expression profiles that correlate with their genotype. These genetic-expression effects should be useful in determining the underlying biology of associations with common diseases of the human brain and in guiding the analysis of the genomic regions involved in the control of normal gene expression