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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 …

Insulin Resistance And T1d: The Effect Of Exercise On Skeletal Muscle Lipid Metabolism, Michelle Dotzert

Electronic Thesis and Dissertation Repository

Insulin resistance is a characteristic of Type 2 Diabetes (T2D) and metabolic syndrome, and until recently has not been considered in the context of Type 1 Diabetes (T1D). A new classification, Double Diabetes, encompasses the presence of insulin resistance in T1D. Unfortunately, these individuals are at significantly higher risk of cardiovascular complications than those with T1D alone. In T2D, abnormal skeletal muscle lipid metabolism and the accumulation of insulin desensitizing lipid metabolites contribute the development of insulin resistance. There is some evidence to suggest this occurs in the context of T1D as well. Exercise training is an effective means to …

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 …

Effect Modification Of The Association Between Aerobic Physical Activity And Diabetes-Related Mortality By Race-Ethnicity: A Population-Based Prospective Study Using Nhanes Iii And 1999-2006 Nhanes, William Robert Boyer Ii

Doctoral Dissertations

Purpose: To examine potential effect modification by race-ethnicity of the relationship between physical activity (PA) and diabetes-related mortality risk using a sample of U.S. adults from the Third National Health and Nutrition Examination Survey (NHANES III). Methods: The sample (n=10,717) included adults (≥20 years) who attended the Mobile Examination Center (MEC). An age-standardized PA score (PAS) was calculated from the self-reported frequency and intensity of 12 leisure-time aerobic activities. The PA scores were then grouped into three categories: inactive (PAS = 0), insufficiently active (PAS >0 - Results: There was no interaction between PA and race-ethnicity (p=0.83). Compared to inactive …

Maternal Diabetes, Related Biomarkers And Genes, And Risk Of Orofacial Clefts, Tiwaporn Maneerattanasuporn

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Orofacial clefts (OFCs) are among the most common congenital birth defects and are characterized by incomplete development of the lip or the palate or both. The lip and palate develop separately at different times during the first trimester of pregnancy. The etiology of OFCs is multifactorial and includes a combination of genetic and environmental factors. This project aims to examine role of maternal diabetes mellitus in orofacial clefts through studies of medical histories, biomarkers, and genes.

In a study of Utah birth certificates, mothers with pre-existing diabetes and gestational diabetes mellitus (GDM) had an increased risk of OFCs, and obese …

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 …

Evaluation Of Berry Extracts On Intestinal Digestive Enzymes And Sugar Transporters, Jungbae Ohrenberger

Masters Theses

T2DM is a chronic disease characterized by postprandial hyperglycemia. One of the therapeutic approaches to attenuate hyperglycemia is to inhibit intestinal ɑ-glucosidase enzyme and/or suppress glucose transporters that regulate intestinal glucose transporters such as SGLT1 & GLUT2. Berries rich in polyphenol antioxidants have various health benefits. Although the antidiabetic effects of various berry extracts or berry mixture in pre-clinical and clinical studies, the underlying pathways at the molecular level is still unclear. In this study, we investigated antioxidant and antidiabetic effects of selected berry extracts by determining free radical scavenging activates, Caco-2 intestinal ɑ-glucosidase activity, glucose uptake and the gene …

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 Effects Of An Acute Bout Of Exercise On Hunger Hormones In Individuals At Risk For Type 2 Diabetes, Sydney Spoon

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Hunger hormone levels are typically dysregulated in obese and diabetic

populations, however; postprandial exercise has been shown to influence hunger hormone levels. Purpose: To determine if hunger hormones including acylated ghrelin and GLP-1 levels are altered in response to an acute bout (15 minutes) of walking in individuals at risk for type 2 diabetes mellitus (T2DM).

Methods: Ten subjects at risk for prediabetes (fasting blood glucose 100–125mg/dL) participated in this randomized crossover design trial. Subjects arrived at the laboratory following an overnight fast and underwent one of two conditions: 1) Test meal with no walking (CON) or 2) Test …

Interfacing Continuous Measurement Of Glucose And Physical Activity To Predict Glycemic Control In Individuals With Type 2 Diabetes, Jennifer Blankenship

Doctoral Dissertations

Physical activity is a cornerstone in the management of hyperglycemia and risk of cardiovascular disease in type 2 diabetes (T2D). However, the dose response relationship between physical activity and glucose regulation is not well defined. The overall goal of this dissertation was to assess the magnitude and timing of changes of daily glucose concentrations in response to continuous and intermittent light physical activity in T2D. Through utilizing continuous glucose monitors (CGM) and physical activity monitoring concurrently, we were able to assess the glycemic impact of physical activity and sedentary behavior in the free-living environment. Study 1 aimed to examine the …

Remote Preconditioning: Evaluating The Efficacy Of Cardioprotection In Type-2 Diabetes And Exploring The Mechanistic Role Of Exosomes, Joseph Michael Wider

Wayne State University Dissertations

Remote preconditioning is a promising and robust treatment for myocardial

ischemia/reperfusion injury that evokes cardioprotection through endogenous neural

and/or humoral signaling. A recent study has reported that protective signaling is

mediated by exosomes through the circulation; however this concept is supported by

limited and inconsistent evidence. Despite overwhelming success in preclinical studies,

the efficacy of remote preconditioning in human studies is inconclusive. Importantly, the

majority of remote preconditioning studies use healthy animal models despite growing

evidence that comorbidities, such as type-2 diabetes, may negatively influence

outcomes. Nonetheless, the efficacy of remote preconditioning in the setting of type-2

diabetes has not …

Human Kinome In Skeletal Muscle Insulin Resistance, Yue Qi

Wayne State University Dissertations

Protein kinases play fundamental roles in regulation of biological processes and functions, such as insulin signaling and glucose metabolism. Dysregulation of protein kinases may cause impaired cell signaling and human diseases, such as metabolic syndrome and type 2 diabetes (T2D). Skeletal muscle is the main site responsible for insulin-stimulated glucose disposal, and insulin resistance in skeletal muscle is one of the key features of the pathogenesis of T2D. Therefore, malfunction of protein kinases and their interaction proteins may contribute to the molecular mechanism of insulin resistance in human skeletal muscle. However, no large scale profiling study has been reported to …

Investigation Into Roseburia Intesinalis For Optimal Growth And Survivability Conditions For Potential Probiotic Use, Lisa Rana Felczak

Wayne State University Theses

Obesity and diabetes is an epidemic of increasing concern. Certain novel bacteria have been found to be an aid in reversing some of the mechanisms associated. This study focused on investigating the optimal stability conditions for R.intestinalis that can associate with an increase in growth. First, environmental conditions were tested to find the optimal conditions associated with each. Once growth conditions were found, generation time was calculated and various prebiotics were used to investigate a potential for additional growth. Next, common antibiotics were tested to see if the R.intestinalis could still show growth when exposed. Large batches of R.intestinalis were …

Protein Phosphatase 2a Function And Regulation In Insulin Resistant Human Skeletal Muscle Cells, Shukurat Sulaiman

Wayne State University Theses

Protein Phosphatase 2A (PP2A), a major serine/threonine phosphatase involved in insulin signaling pathway, plays a critical role in the development of insulin resistance and type 2 diabetes (T2D), which is characterized with hyperinsulinemic hyperglycemic condition. Moreover, majority of the glucose disposal takes place in the skeletal muscle which is also the main tissue responsible for insulin resistance. The catalytic subunit of PP2A (PP2Ac) can interact with multiple regulatory subunits and other regulatory proteins as well as substrates. These interactions are important for maintain normal PP2A function and subsequent cell signaling. We hypothesized that hyperinsulinemic hyperglycemic condition and insulin stimulation would …

The Effect Of Yoga Practice On Glucose Control, Physiological Stress, And Well-Being In Type 2 Diabetes: Exploring A Mechanism Of Action, Maricarmen Vizcaino

Open Access Theses & Dissertations

Multiple studies have found yoga practice to be effective in improving glucose control and other health markers of adults with type 2 diabetes mellitus (T2DM). However, current findings cannot reach a consensus given multiple methodological inconsistencies. The primary purpose of this Dissertation work was to investigate the impact of yoga practice on the glucose control of participants with T2DM through two different approaches in two separate exploratory studies. The first study, a quasi-experimental design, examined the effect of eight weeks of yoga practice on glucose control taking into account previous limitations in the literature. The second study, a single-subject design, …

Effects Of Posttranslational Modification Of Transcription Factor Gli-Similar 3 By Sumoylation On Insulin Transcription In Pancreatic Β Cells, Tyler M. Hoard

Murray State Theses and Dissertations

The ability to control blood glucose levels is a fundamental component of vertebrates. In these organisms, blood glucose homeostasis is achieved through a fine-tuned mechanism that largely involves the secretion of hormones from the endocrine pancreas into the bloodstream. These hormones include glucagon, which is secreted by the α cells of the pancreas and initiates the release of glucose into the bloodstream through gluconeogenesis in the liver, and insulin, which is secreted from the β cells and signals the uptake of excess blood glucose by the peripheral tissue. Gli-similar 3 (Glis3) is a transcription factor that has previously been shown …

Assessing For Awareness And Knowledge Regarding Diabetes In Pre-Diabetes Obese Patients, Remona Lysa Brown

Walden Dissertations and Doctoral Studies

Over the past few decades, there has been an increase in prevalence of diabetes in the United States. Prevention of diabetes and improving patients' knowledge and awareness of diabetes are crucial for healthcare providers. Using the Health Belief Model (HBM) as a theoretical foundation, the student used the National Diabetes Prevention Program (NDPP) from the Centers for Disease Control and Prevention (CDC), to improve awareness and knowledge of diabetes among obese individuals with prediabetes. The key research question of this project was to determine whether the patients' diabetes knowledge and awareness improved after the NDPP program. A convenience sample of …

Diabetes-Induced Expression And Regulation Of Glp-1 Levels By Bile Acid Receptors (Tgr5 & Fxr), Joseph R. Spengler

Theses and Dissertations

Diabetes Mellitus has continued to drastically affect the health of the world and many complications can prove fatal. As long as this metabolic disease persist, research discoveries will need to continue to be made so that patient outcomes and healthcare are dramatically enhanced. In recent years, GLP-1 has been the topic of conversation for diabetes research, due to its promising effects in promoting insulin sensitivity. Furthermore, bile acids and their receptors (TGR5 & FXR) have shown promise in their actions in the regulation of GLP-1, and thus glucose homeostasis. Here we have shown the detection and increased expression of TGR5 …

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 …

Effect Of Hyperglycemia And Thiazolidinediones On Cardiac Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Db/Db Diabetic Mice., Rucha Fadnavis

Browse all Theses and Dissertations

Type 2 diabetes mellitus is strongly associated with increased risk of cardiovascular disease. Despite availability of several antidiabetic medications, the cardiovascular outcomes remain unchanged. Activation of renin angiotensin system is one of the critical factors in development of diabetic complications. Hyperglycemia causes an increase in tissue and circulating Angiotensin II. Angiotensin converting enzyme (ACE2) and neprilysin (NEP) are angiotensin (1-7) forming enzymes. ACE2 was first cloned from heart failure patients and has cardioprotective and renoprotective properties. Combination of angiotensin receptor antagonism and NEP inhibition is a new therapeutic strategy for treatment of heart failure. The aim of this study was …

Effect Of Hyperglycemia And Thiazolidinediones On Cardiac Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Db/Db Diabetic Mice, Rucha Fadnavis

Browse all Theses and Dissertations

Type 2 diabetes mellitus is strongly associated with increased risk of cardiovascular disease. Despite availability of several antidiabetic medications, the cardiovascular outcomes remain unchanged. Activation of renin angiotensin system is one of the critical factors in development of diabetic complications. Hyperglycemia causes an increase in tissue and circulating Angiotensin II. Angiotensin converting enzyme (ACE2) and neprilysin (NEP) are angiotensin (1-7) forming enzymes. ACE2 was first cloned from heart failure patients and has cardioprotective and renoprotective properties. Combination of angiotensin receptor antagonism and NEP inhibition is a new therapeutic strategy for treatment of heart failure. The aim of this study was …

Po2 Dependence Of Oxygen Consumption In Skeletal Muscle Of Diabetic And Non-Diabetic Rats, Alexander C. Liles

Theses and Dissertations

Abstract

PO₂ DEPENDENCE OF OXYGEN CONSUMPTION IN SKELETAL MUSCLE OF DIABETIC AND NON-DIABETIC RATS

By: Alexander C. Liles

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at the Medical College of Virginia Campus, Virginia Commonwealth University

Virginia Commonwealth University, 2017

Advisor: Roland N. Pittman, Ph.D.

Department of Physiology and Biophysics

Type 2 diabetes mellitus (T2DM) is a major medical problem around the world, affecting nearly 6% of the world’s population. This study was an attempt to better understand physiological changes the disease may cause to the microcirculation and more specifically, to …

Oxidative Stress And Proteomic Studies Of Mammalian Models Of Age-Related Metabolic Dysfunction In Neurodegenerative Disorders, Aaron M. Swomley

Theses and Dissertations--Chemistry

Expression proteomics is the field of science wherein proteins that make up the cellular proteome are identified both by name and by fold-change. Depending on the application of proteomics, this change in level could be due to internal cellular stressors or introduction of xenobiotics. Global oxidative stress measures use immunohistochemistry to determine the relative level of oxidative stress of macromolecules within the cell. In this dissertation, both global oxidative stress measures and expression proteomics were used in a variety of mammalian models in order to determine the effects of protein upregulation, intranasal insulin administration, and resveratrol supplementation on the cellular …