Biochemistry, Biophysics, and Structural Biology Commons^™

On The Relationship Of Diabetes And Sleep Apnea: Evolution And Epigenetics, Nancy Wilson

Undergraduate Honors Theses

This thesis gives an overview of the relationship between diabetes, sleep apnea, obesity, and heart disease. It then addresses evidence that the traditional understanding of this relationship is incomplete or misleading. In the process, there is a brief discussion of the evolutionary rationale for the development and retention of sleep apnea in light of blood sugar dysregulation, as an adaptive mechanism in response to environmental stressors, followed by a brief overview of the general concepts of epigenetics. Finally, this paper presents the results of a literature search on the epigenetic marks and changes in gene expression found in sleep apnea …

Using Crispr-Cas9 To Characterize The Role Of Gli-Similar 3 (Glis3) In Insulin Regulation, Pancreatic Development, And Type 2 Diabetes, Lilyanne Grieve

Honors College Theses

The prevalence of type 2 diabetes continues to rise nationally and internationally, impacting millions of people worldwide. Type 2 diabetes results from insulin resistance leading to chronic hyperinsulinemia and dysfunction of the insulin producing β cells of the pancreas. While environmental factors can influence the development of type 2 diabetes, research has shown genetics are also involved. Gli-similar 3 (Glis3), a Krüppel-like zinc finger transcription factor, has been identified as a novel regulator of insulin transcription. Evidence has shown that loss-of-function Glis3 mutations decrease insulin expression, implicating Glis3 in the development of type 2 diabetes. However, the distinct role Glis3 …

Building An Ins-1 Cdna Library For A Genome-Wide Crispr-Cas9 Screen, Idongesit Ekpo

Undergraduate Honors Theses

By the year 2040, an estimated 642 million people are expected to have diabetes globally. Diabetes results from an elevation of metabolic stressors, such as glucotoxicity, lipotoxicity, oxidative stress and apoptosis. In type 2 diabetes, these stressful conditions contribute to the malfunction and loss of functional insulin-producing β-cells. Current treatment methods for diabetes include insulin therapy, islet transplant and anti-diabetes medication. These treatments are not curative and ignore other factors that contribute to the pathogenesis of diabetes beyond insulin resistance and islet β-cell failure. Previous research on β-cells has focused on ways to replace functional β-cell mass, trigger β-cell proliferation, …

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products), which bind …

Role Of Microrna-483 In Pancreatic Β-Cells, Jackson Waugh

Dissertations, Master's Theses and Master's Reports

Insulin is an essential hormone produced by β-cells in the pancreas. The release of insulin is tightly regulated in healthy people in order to control blood sugar level in our body. However, people with Type 2 Diabetes have insufficient insulin secretion from pancreatic β-cells, leaving to high blood sugar (hyperglycemia) and β-cell failure. microRNAs (miRNAs or miR) are newly discovered small regulatory molecules and have emerged as important regulator of cell growth, differentiation, and organ function. Altered miRNA function has been implicated in the pathogenesis of a variety of human disease, including diabetes. In this report, we focus on dissecting …

Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau

Legacy Theses & Dissertations (2009 - 2024)

Diabetes is a global health epidemic that can be devastating to those afflicted,

Understanding The Rage Signaling Pathway And Its Contribution To Diabetic Complications, Leon Vegas Ho

Legacy Theses & Dissertations (2009 - 2024)

The binding of advanced glycation end products (AGEs) to the receptor for advanced glycation end products (RAGE) is an important feature of the RAGE signaling pathway that plays a role in the pathogenesis of diabetes. Under high glucose concentration, RAGE expression increases immensely from the formation of a Schiff base by glucose bounded to lysine. This triggers an inflammatory and immune response and upregulates the expression of RAGE and causes an accumulation of AGEs in the body. As a result, this leads to the development of diabetes and other complications such as, atherosclerosis, nephrothapy, and retinopathy. To remedy AGE accumulation, …

In Vitro Investigation Of The Effect Of Camel Milkproteins And Its Fractions On Insulin Receptor Function, Arshida Ashraf

Biology Theses

Camel milk (CM) has been reported to have anti-diabetic properties in many in vitro and in vivo studies but the molecular basis of such beneficial properties are still elusive. Recently, camel milk whey proteins (CWPs) have been shown to positively affect the activity of the human insulin receptor (hIR) in cell lines. In this study, we profiled crude CWPs and their hydrolysates as well as camel milk lactoferrin (CMLF) for their pharmacological and functional effects on hIR activity and its downstream signaling in both human embryonic kidney (HEK293) and hepatocarcinoma (HepG2) cell lines. For this, bioluminescence resonance energy transfer (BRET) …

Yczr, A New Case Of Plp-Dependent Mocr/Gabr Type Transcription Regulator In Klebsiella Pneumonia, Yuanzhang Zheng

Dissertations

Increasing number of genes encoding PLP-dependent transcription regulators, MocR/GabR type regulators, have been identified in various bacterial genomes. However, only a handful of them, including MocR, PdxR and GabR have been studied experimentally. They control different aspects of the bacterial metabolism. Only GabR has reported crystallographic structures. MocR/GabR regulators possess a chimeric structure consisted of a WHTH DNA binding domain and an Aminotransferase-like regulation domain, which can bind PLP as an effector in transcription regulation. Such a chimeric construct presents an interesting case in molecular evolution. The regulation domains of All MocR/GabR type regulators loss their catalytic capacity during evolution …

Interrogation Of Protein Function With Peptidomimetics, Olapeju Bolarinwa

USF Tampa Graduate Theses and Dissertations

Proteins can be described as the “machineries” responsible for almost all tasks in the levels of organizational complexity in multi-cellular organisms namely: the cells, tissues, organs and systems. Any disorder in the function of a protein at any of these levels could result in disease, and a study of protein function is critical to understanding the pathological features of the disease at the molecular level. A quick glance at these abundantly present proteins reveals two striking features: large diversity of biological function, and the variations in structural complexity, which varies from simple random coils, to turns and helices, and on …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations & Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …

Biomedical Applications Of Mid-Infrared Spectroscopic Imaging And Multivariate Data Analysis: Contribution To The Understanding Of Diabetes Pathogenesis, Ebrahim Aboualizadeh

Theses and Dissertations

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of adult vision loss. Although a great deal of progress has been made in ophthalmological examinations and clinical approaches to detect the signs of retinopathy in patients with diabetes, there still remain outstanding questions regarding the molecular and biochemical changes involved. To discover the biochemical mechanisms underlying the development and progression of changes in the retina as a result of diabetes, a more comprehensive understanding of the bio-molecular processes, in individual retinal cells subjected to hyperglycemia, is required. Animal models provide a suitable resource for temporal detection …

Evidence Of A Perilipin 5 Splice Variant, Brodie Ranzau

Undergraduate Honors Thesis Projects

Alternative splicing occurs throughout the human genome, leading to multiple proteins from a single gene. The resulting proteins can be nearly identical or vastly different in how they function. Alternative splicing within the perilipin family has been observed in perilipins 1 and 3, giving rise to proteins with varying functions. In the course of our studies on perilipin 5, an immunoblot signal was observed that corresponded to an approximately 35 kDa protein. Western blot analysis of this protein has revealed its expression in C2C12 cultured myoblasts and in heart and liver mouse tissue. Further analysis of perilipin 5 cDNA through …

Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying

Honors Thesis

The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the metals were not inhibiting IAPP …

Study Of Protein-Protein Interaction By Using In-Cell Nmr In Human Cells, Asma Salem M Aldousary

Legacy Theses & Dissertations (2009 - 2024)

We developed a new technology to study protein-protein interaction in mammalian cells. This technology is based high resolution of Nucleic Magnetic Resonance (NMR) spectroscopy. Using this technology we studied interaction between the receptor for advanced glycation endproducts (RAGE). RAGE- is a multiligand receptor of immunoglobulin receptor family that is activated by a multitude of ligands. Activation of RAGE results in signal transduction that leads to the inflammatory response implicated in the complications of Diabetes. RAGE is an emergent drug target that has been explored for the variety of pathologist including cancers, neurological disorders, inflammatory disease, and diabetes. and Intracellular effector …

Expression Of Insulin Responsive Genes In Insulin Resistant Conditions, And The Effect Of Selenium On Gene Expression, David L. Ruff

Masters Theses

Chronically high blood glucose levels lead to many problems, such as insulin resistance, the hallmark of Type II diabetes. Increased flux through the hexosamine biosynthesis pathway is one mechanism by which high glucose as well as glucosamine has been shown to induce insulin resistance. This study tests the effects of glucosamine induced insulin resistance on insulin regulation of the metabolic genes glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) as well as insulin responsive proteins tribbles homolog (TRIB3) and sterol regulatory element binding protein (SERBP-1c) 1c.

Selenium, a micronutrient has been shown to be an effective insulin mimetic in Type …

Characterization And Diurnal Measurement Of Oral Inflammation In Association With Glycemic Control, Periodontal Status, & Glucose Stimulation, Melanie N. Kuehl

USF Tampa Graduate Theses and Dissertations

Diabetes has afflicted 8.3%, approximately 25.8 million, of the United States population and is the seventh leading cause of death [1]. Type I diabetes (T1D) accounts for 5 to 10% of all diagnosed cases of diabetes in the United States [2]. If present trends continue, the rate of T1D incidence among children under the age of 14 will increase by 3% globally [3]. T1D is an autoimmune disorder in which the β-cells of the pancreatic islets are destroyed, leading to high blood sugar. Hyperglycemia and loss of immunological tolerance to self-antigens are common associations of T1D [4]. Periodontal disease impacts …

Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton

Renée Crown University Honors Thesis Projects - All

Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.^1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working …

Investigation Into The Cellular Actions Of Carnosine And C-Peptide, Emma H. Gardner

Theses, Dissertations and Capstones

Carnosine is a dipeptide composed of beta-alanine and histidine found exclusively in long-lived animal tissues. The cellular action of carnosine is still under extensive investigation; however, it has been proposed to have a role as an anti-oxidant and oxygen free radical scavenger, a physiological buffer, a heavy metal chelator, and has been implicated as an anti-aging agent.^2,4 Our lab has been studying the interaction between carnosine and heme by analyzing both the effect carnosine has on the glycation of the heme containing protein cytochrome c and the interaction of carnosine with free hemin. We have observed that the addition …

Leptin Resistance Induced Obesity And Diabetes Promote Neuropathological Changes In The Aging Brain, Thomas Platt

Theses and Dissertations--Molecular and Cellular Biochemistry

The aging brain is prone to the development of pathology and dementia. With a rapidly growing elderly population diagnoses of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease are on the rise. Additionally, diabetes and obesity are linked to an increased risk of dementia. The convergence of this increasingly aged population with the obesity and diabetes epidemic give rise to new concerns regarding the future of prevention and treatment of neurodegenerative diseases. Our lab has previously shown that leptin, an adipokine involved in signaling satiety to the hypothalamus, can modulate the generation of the amyloid …

Bone Morphogenetic Protein-7 Attenuates Inflammation And Apoptosis And Improves Cardiac Function In Diabetes, Princess Urbina

Electronic Theses and Dissertations

Bone Morphogenetic Protein-7 (BMP-7) belongs to the transforming growth factor-β (TGFβ) family of cytokines has is known to have potent anti-inflammatory properties. It has been used in patients to treat osteoporosis clinically and has been reported to treat diabetic nephropathy in murine models. Moreover, studies show that inflammation is up-regulated in patients with pre-diabetes (PD). We, therefore, hypothesize that the administration of BMP-7 will attenuate inflammation in the heart of Streptozotocin (STZ)-induced PD mice. In this study, we divided C57Bl/6 mice into three groups: CONTROL, PD, and PD+BMP-7. CONTROL mice received intraperitoneal (i.p.) injections of Sodium Citrate Buffer while PD …

Low Cost Production Of Proinsulin In Tobacco And Lettuce Chloroplasts For Injectable Or Oral Delivery Of Functional Insulin And, Diane Burberry

Electronic Theses and Dissertations

Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, and C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene and homoplasmy. Old tobacco leaves accumulated proinsulin up to 47% of total leaf protein (TLP). Old lettuce leaves accumulated proinsulin up to 53% TLP. Accumulation was so stable that up to …

Alpha-Msh Regulated Cell Signaling In Pancreatic Alpha Cells, Liang Liang

Electronic Theses and Dissertations

Peripheral injection of α-MSH promotes glucagon secretion in POMC knockout mice, suggesting the role of α-MSH in regulation of pancreatic α cells. However, the underlying mechanisms remain unknown. This study investigated the stimulatory effect of α-MSH on mice pancreatic α cell line αTC1-6 cells in cell signaling pathway as well as glucagon secretion. In normal level of glucose, application of α-MSH stimulated Ltype Ca2+ current induced Ca2+ induced Ca2+ release (CICR) and membrane hyperpolarization. Increase of [cAMP]c was also observed when α-MSH was applied with IBMX. Acute hypoglycemia-induced CICR via N- and L-type Ca2+ channels was overridden by typical α-MSH …

Chromosomal Localization Of The Islet Neogenesis Associated Protein (Ingap) Gene In Syrian Hamster By Tyramide Signal Amplification-Fluorescence In Situ Hybridization (Tsa-Fish), Sallie A. Smith

Biological Sciences Theses & Dissertations

Diabetes mellitus is a group of conditions characterized by hyperglycemia due to an inability to produce or properly utilize insulin. The majority of cases fall into two categories, Type I and Type 2. Type I results from the autoimmune destruction of pancreatic β-cells of the islets. The beta cells are the exclusive source of insulin and the patient becomes entirely dependent on exogenous insulin to survive. Patients with Type 2 are distinguished by insulin resistance, a condition that develops due to the inability of the body to effectively use the insulin being produced. The β-cells gradually lose their ability to …

Abnormalities In Post-Translational Processing Of Platelet Rap 1b In Niddm: A Possible Cause Of Platelet Hyperactivity And Cardiovascular Disease In Diabetes, Elizabeth Ann Hall

Theses and Dissertations in Biomedical Sciences

Post-translational processing is critical for the appropriate subcellular localization and function of platelet G-proteins. The majority of the platelet responses to agonists are mediated through specific receptor/G-protein complexes. Therefore, G-protein activity is central to "normal" platelet activity (i.e. aggregation). We have shown that Simvastatin, the in vivo inhibitor of HMG CoA Reductase and therefore isoprenoid synthesis, inhibits the post-translational processing of specific platelet G-proteins and alters platelet responses to agonists. These results show the importance of post-translational processing of G-proteins to platelet activity. Altered post-translational processing of specific G-proteins may explain platelet hyperactivity and the increased incidence of cardiovascular disease …