Medicine and Health Sciences Commons^™

Investigation Of Heterocyclic Amines And N-Acetyltransferase 2 Genetic Polymorphism In The Dysregulation Of Hepatic Energy Homeostasis: A Gene-Environment Approach., Kennedy M Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are mutagens generated when cooking meat for prolonged periods of time or until well-done. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. However, no previous studies have examined if HCAs, independent of meat consumption, contributes to pathogenesis of insulin resistance or metabolic disease. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans that, depending on the combination of NAT2 alleles, correlate to rapid, intermediate, or slow acetylator phenotypes that exhibit differential …

Telehealth In Patients With Type 2 Diabetes Mellitus, Saghi Nassrouie

UNLV Theses, Dissertations, Professional Papers, and Capstones

Description: Type 2 diabetes mellitus (DM2) is an epidemic that has many factors involved in its management to maintain control. Patients with DM2 require routine evaluations and blood work to provide comprehensive care. COVID-19 caused major shifts in traditional care which sparked an increase in the utilization of technology like telehealth. Telehealth can be an effective tool used to manage diabetes and help attain better glucose control, but its effectiveness during the COVID-19 pandemic warrants further investigation.Purpose: The purpose of this project was to determine if telehealth visits were more effective in reducing Hemoglobin A1c (HbA1c) in adult patients with …

Prevention Of Obesity-Related Morbidity & Mortality In Adults, Rachelle Virgin

Masters Theses/Capstone Projects

Poster presentation on the prevention of obesity related morbidity and mortality in adults.

An Evaluation Of A Multidisciplinary Implementation Of Evidence Based Practice In Prediabetes, Emily Sisco

Dissertations

Abstract

Problem Over 70% of prediabetic patients progress to full diabetes. There are over 80 million American adults who are diabetic. Diabetes is the costliest chronic disease that often leads to many other health issues.

Methods This QI project utilized a descriptive observational design. Quantitative data was collected via retrospective chart review. Primary data collected was documentation of a patient visit to the registered dietician and the hemoglobin A1c (HbA1c) of patients who followed up in the office after the referral.

Results Eight patients followed up to the office for a second visit (n=8). Four patients did see the registered …

The Requirement Of Transcriptional Lim Complex Co-Regulators For Pancreatic Endocrine Cell Development And Function, Eliana Davi Toren

All ETDs from UAB

The prevalence and tremendous impact of diabetes mellitus has made glucose regulation of the insulin-producing -cell and surrounding pancreatic islet of Langerhans a center of public and research interests alike. A comprehensive understanding of these hormone-producing cells begins with their developmental origins. What are the genetic cues and participants in the tightly orchestrated process of their formation? Investigating the earliest determinants of islet-cell fate not only allows us to deeply understand mature - and islet-cell function, but also produces a data-driven template for how these cells can be reproduced in future stem-cell based diabetes therapies. LIM transcriptional complexes are indispensable …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie

Theses, Dissertations and Capstones

Diabetic skin wound is a common complication of diabetes that occurs in about 15% of diabetic patients and often requires prolonged hospitalization for its management and treatment. Natural polymers are used for wound dressing due to their biological adhesiveness, non-toxicity, and biodegradable nature. 5-Fluorouracil (FU) has been shown to alter adipokine expression which is implicated in cutaneous wound repair. Thus, our overall objective was to investigate the utility of chitosan (CS) gel for topical delivery of 5-FU to treat diabetic wounds. We prepared chitosan gel (2% w/w) in serial dilutions of 5-FU (25μg/mL, 2.5μg/mL, 0.25μg/mL, and 0.025μg/mL) and evaluated their …

Role Of Thymidine Phosphorylase In Type 2 Diabetes-Associated High-Risk Of Thrombosis, Adam Belcher

Theses, Dissertations and Capstones

Cardiovascular diseases (CVDs), such as ischemic heart disease and stroke, are the leading causes of death globally that disproportionally affects patients with type 2 diabetes mellitus (T2DM) at a 2-4-fold rate compared to non-diabetic patients. These CVDs result from a blood clot, also known as a thrombus, formed in arteries that can block blood flow resulting in tissue damage and death. Antiplatelet drugs, such as aspirin and clopidogrel, used to prevent thrombosis have been found to be less effective in diabetics and increase the risk of hemorrhagic events. The T2DM epidemic has made it imperative to find therapies that decrease …

Metabolic And Electrophysiological Effects Of Fibroblast Growth Factor 19 In The Dorsal Vagal Complex, Jordan Wean

Theses and Dissertations--Physiology

The dorsal vagal complex (DVC) is an important homeostatic regulatory center located in the hindbrain that alters vagal parasympathetic activity in response to central, viscerosensory, and humoral cues. Within the DVC, second-order sensory neurons in the nucleus tractus solitarius (NTS) integrate ascending vagal sensory input with descending regulatory inputs from higher brain areas and respond to circulating hormones and glucose. In turn, the NTS projects to the dorsal motor nucleus of the vagus (DMV) which is comprised of cholinergic motor neurons and regulates gastric motility, hepatic glucose production, and pancreatic hormone release functions, among others.

Fibroblast growth factor 19 (FGF19) …

Gut Microbiota And The Development Of Type 2 Diabetes, Janet Ryan

Nursing | Senior Theses

This paper explores the question: Can interventions focusing on healing the gut microbiome of a prediabetic patient prevent or delay the onset of type 2 diabetes? Diabetes is a major health problem that is becoming the biggest epidemic of the 21^st century. Efforts to derail the progression of disrupted blood glucose metabolism are often futile leaving patients frustrated with a lifelong burden of disease management. Recent studies suggest that collectively the gut microbiome acts as an endocrine organ and that injury to this “organ” can lead to dysfunctional glucose regulation. A comprehensive literature review revealed that further studies are …

Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea

All ETDs from UAB

The Ldb1:Isl1 LIM transcriptional complex is critical for endocrine pancreas development as well as b-cell terminal differentiation. These complexes have been shown to interact with various proteins to elicit transcriptional regulation in other tissues, yet few interactors have been identified in b-cells. Therefore, the objective of this dissertation was to identify interactors of Ldb1 and Isl1 and assess their contributions to endocrine pancreas development and function. Using a reversible crosslink immunoprecipitation (ReCLIP) and mass spectrometry (MS) strategy to isolate endogenous Ldb1 and/or Isl1 interacting protiens, SSBP3, Rnf20, and Rnf40 (E3 ubiquitin ligases) coregulators were identified. SSBP3 was found to interact …

Environmental Regulation Of The Heart: The Role Of Non-Coding Rna And Epigenetics In Influencing Mitochondrial And Cellular Health, Quincy Alexander Hathaway

Graduate Theses, Dissertations, and Problem Reports

The mitochondrion, a small but ubiquitously distributed organelle in the cell, continues to be the focus of many disease pathogeneses, tissue and organ dysfunctions, and other morbidities that occur throughout the body. The purpose of this work was to understand how cardiac mitochondrion are altered in disease and pathological states, specifically in their adaptation to environmentally stimulated regulatory networks, such as epigenetic modifications and promotion/inhibition of non-coding RNAs. Acute stress to mitochondrial regulation (inhalation toxicology) as well as chronic (type 2 diabetes mellitus) was examined. Using a FVB transgenic microRNA-378a mouse knockout model, the cardiovascular impact derived from altering the …

Parasympathetic Nerve Derived Exosomes Inhibit Hyperglycemia Induced Apoptosis In Cardiomyoblast Cells, Reetish K. Singla

Honors Undergraduate Theses

Diabetic cardiomyopathy involves both forms of cardiac cell cell death such as apoptosis and necrosis. However, this remains unknown whether hyperglycemia induced apoptosis in the cell culture system is inhibited by parasympathetic nerve derived exosomes. We isolated parasympathetic and sympathetic nerves and derived exosomes. We developed hyperglycemia induced apoptosis in H9c2 cells. H9c2 cells were divided into 4 groups: 1) Control, 2) H9c2+ Glucose 100 mmol, 3) H9c2+ Glucose +parasympathetic-exo, 4) H9c2+ Glucose+sympathetic-exo. We determined cell proliferation and viability with MTT assay kit and apoptosis with TUNEL staining and cell death detection ELISA kit. Data was further confirmed with pro-apoptotic …

Proteomic Characterization Of Human Multipotent Stromal Cells Secreted Proteins With Therapeutic Potential For Β-Cell Regeneration, Miljan Kuljanin

Electronic Thesis and Dissertation Repository

Novel strategies to stimulate the expansion of β-cell mass in situ are warranted for diabetes therapy. Cell-replacement therapies for the treatment of diabetes have become a focal point in recent years. Endogenous regeneration of β-cell mass has been demonstrated using human multipotent stromal cells (hMSC). However, the secretory factors responsible for initiating endogenous regeneration remain unknown. Successful large-scale proteomic applications to address these questions have been limited in part by difficulties in correctly selecting the appropriate methodologies. Thus, the goal of this thesis was a combination of assessing different proteomic workflows to facilitate investigation into hMSC biology, applying these methods …

A Clinico-Pathological Study Of The Structural And Functional Changes In The Retina And Optic Nerve Following Diabetic Retinopathy Treatments, Richard Filek

Electronic Thesis and Dissertation Repository

Diabetic retinopathy (DR) is the result of microvascular changes in the retina due to hyperglycemia which alter the blood-retinal barrier (BRB). The increased permeability of BRB results in the accumulation of extracellular fluid, the development of diabetic macular edema (DME) and capillary occlusion. Capillary occlusion results in retinal ischemia which increases vascular endothelial growth factor (VEGF) levels, increases vascular permeability and results in neovascularization in proliferative diabetic retinopathy (PDR) patients. The treatments clinically used for DR are panretinal photocoagulation (PRP) for PDR and injectable vascular endothelial growth factor inhibitors (anti-VEGFs) for DME.

The safety of PRP and anti-VEGF therapy on …

Retinoic Acid Pathway Inhibition To Expand Human Hematopoietic Progenitor Cells With Islet Regenerative Capacity, Ruth Elgamal

Electronic Thesis and Dissertation Repository

Cellular therapy to induce islet regeneration is emerging as a novel treatment strategy for diabetes. Umbilical cord blood (UCB)-derived hematopoietic stem/progenitor cells (HSPC) isolated by high aldehyde dehydrogenase activity (ALDH^hi) reduce hyperglycemia after transplantation into streptozotocin (STZ)-treated NOD/SCID mice. However, UCB-derived ALDH^hi cells are rare and expansion without the loss of regenerative function is required. We hypothesized that BMS 493, an inverse retinoic acid receptor agonist, will prevent HSPC differentiation of HSPC during expansion, generating more ALDH^hi cells for therapy. ALDH^hi cells expanded for 6 days with BMS 493 showed a 2.70-fold-increase in ALDH^{hi …}

Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris

Arts & Sciences Electronic Theses and Dissertations

Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …

An Evaluation Of Gabab Receptors On Modulating Neuroinflammation In A Non-Transgenic Animal Model Of Alzheimer's Disease, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and distinct neuropathological hallmarks, including amyloid beta plaques and neurofibrillary tau tangles (NFT). Although the etiology remains to be discovered, several risk factors exist that significantly contribute to developing AD. Diabetes is one of the major risk factors associated with AD and is characterized by disrupted insulin signaling that may contribute to or exacerbate AD pathologies. Furthermore, both disorders result in increased neuroinflammation. Considerable evidence has demonstrated that a chronic inflammatory response, in particular chronic microglia activation, promotes A production as well as the hyperphosphorylation of tau through …

The Long Non-Coding Rna Malat1 Regulates Inflammatory Cytokine Production In Chronic Diabetic Complications, Andrew D. Gordon

Electronic Thesis and Dissertation Repository

We examined the role of MALAT1, a highly conserved nuclear lncRNA, in chronic diabetic complications affecting the heart and kidneys, specifically with respect to inflammatory cytokine production. Endothelial cells, exposed to various glucose levels, and MALAT1 knockout mice and controls, with or without streptozotocin-induced diabetes were examined. Endothelial cells cultured with high glucose, and renal and cardiac tissue from diabetic mice showed increased inflammatory cytokine (eg. IL-6, IL1β, TNFα) production along with transient MALAT1 upregulation. This was confirmed by both transcript and protein analyses, and such changes were prevented in the MALAT1 knockout diabetic animals. In the malat1 knockout animals, …

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …

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 …

Determining The Effect Of Knocking Out Microrna-21 On Subsarcolemmal And Interfibrillar Mitochondria, Madhur Batra

Theses and Dissertations

Type 2 diabetes mellitus is a growing problem across the world and has significant pathological changes associated with it, including diabetic cardiomyopathy, wherein cardiac function is reduced. MicroRNA-21 has been shown to play a role in both the heart and diabetes so it was thought that knocking out miR-21 could have a protective effect on oxidative phosphorylation function in diabetic mice. Subsarcolemmal and interfibrillar mitochondria were isolated from adult male WT, miR-21 KO, db/db, and double knockout mice (db/db and miR-21 KO cross) and evaluated for function. Knocking out miR-21 in diabetic mice showed a restorative effect in Complex I …

Diabetic Ketoacidosis, Mario Bianconi

Nursing Student Class Projects (Formerly MSN)

According to “Statistics About Diabetes” (2014), in 2012, 29.1 million Americans, or 9.3% of the population, had diabetes. Additionally, of the 29.1 million, 21 million of the population were diagnosed, and 8.1 million were undiagnosed. With such a high prevalence, it is imperative that the hospital nurse is aware not only how to treat diabetes, but also how to look for complications of diabetes. One of the severe complications of diabetes is Diabetic Ketoacidosis, or DKA. DKA occurs as a result of prolonged untreated diabetes. It is the result of the body not being able to produce, or use, insulin …

Diabetic Prevention The Hard Way: Modified Diet And Increased Exercise, Torrie Reese St.Julien

Doctor of Nursing Practice Final Manuscripts

Background and Purpose: In the United States, 79 million people are pre-diabetic: most have no symptoms. If left untreated, 37% will develop diabetes within 4 years. Fourteen percent of United States health care expenditures are related to diabetic complications. This Evidenced Based Project (EBP) involved a behavioral lifestyle change with the purpose of 7% weight loss and a minimum of 150 minutes of physical activity a week. It was also designed to reduce risk factors and glycated hemoglobin A1c (HgA1c) levels.

Methods: The interventional approach was modeled after the Diabetes Prevention Program (DPP) and Group Lifestyle Balance Program. Participants were …

Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton

Honors Capstone 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 …

Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin

Electronic Thesis and Dissertation Repository

ii Abstract Abstract Defects in the proliferation, differentiation, and activity of bone marrow (BM)-derived vasculogenic/vascular stem cells (VSCs) have been observed in diabetes and contribute to the development of vascular complications. Diabetes leads to enhanced bone marrow adipogenesis, altering the composition of the BM stem cell (SC) niche and potentially disrupting the normal functioning of resident VSCs. Here, I establish that adipocytes have a negative influence on SC survival in culture. I also show that adipocytes and osteoblasts are responsible for the creation of distinct extracellular microenvironments, with unique expression patterns of several pro- and anti-angiogenic factors with known effects …

Pancreatic Beta Cell Plasticity And Involvement Of Insulin-Expressing Progenitor Cells, Christine A. Beamish

Electronic Thesis and Dissertation Repository

Islet transplants have been successfully used as treatment for diabetes, but are limited by shortages of cadaveric insulin-producing β-cells. An alternate source may be the dedifferentiation, expansion, and subsequent redifferentiation of pancreatic islets or β-cells using in vitro techniques prior to transplant. Based on protocols which described the dedifferentiation of human islets to ductal-like cells, we hypothesized that neonatal mouse islets could be similarly dedifferentiated in vitro. Dedifferentiation techniques produced significant duct-like cells, but redifferentiation to insulin-expressing cells was limited. RIPCre;Z/AP+/+ mice were consequently utilized to lineage trace β-cell fate during culture by a human placental alkaline phosphatase (HPAP) reporter. …

Management Of A Dka Patient With Severe Metabolic And Ketoacidosis With Chronic Renal Insufficiency, Brian Albany

Nursing Student Class Projects (Formerly MSN)

Diabetic ketoacidosis (DKA) serves as one the leading causes of mortality in diabetic patients [14]. The mortality has decreased over the past several decades due to the rapid recognition of the disease state and the improvement of management of DKA [14]. Despite a decline in mortality rates over the past twenty years from 7.96% to 0.67%, errors in management of the disease state are associated with significant morbidity and mortality [2]. Utilization of DKA protocols in the acute care setting have allowed congruency in care and delivery of effective lifesaving treatment. Despite advances in standardized DKA protocols, there still remains …

Incretin Hormones And Their Effects In Type 2 Diabetes, Molly Getz

Nursing Student Class Projects (Formerly MSN)

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized as having pancreatic β-cell dysfunction, insulin resistance and hyperglycemia (Stephens, 2010, p. 491). T2DM affected 29.1 million Americans or 9.3% of the population in 2012 and was the seventh leading cause of death in the United States in 2010 ("ADA Statistics," 2014), with many of these patients finding it difficult to achieve or maintain adequate glycemic control despite making lifestyle changes and pharmacologic interventions (Freeman, 2007). Disease management of T2DM requires a comprehensive plan including medication therapy, education and active involvement of the patient, with the goal of therapy to …