Biochemistry Commons^™

New Emerging Roles Of The Novel Hepatokine Serpinb1 In Type 2 Diabetes Mellitus: Crosstalk With B-Cell Dysfunction And Dyslipidemia, Mohamed M. Kamal, Aya A. Ali, Ghada H. Sayed, Shadia Ragab, Dina H. Kassem

Pharmacy

Diabetes mellitus (DM) is a devastating metabolic disease. Recently, the cross-talk between insulin-secreting-β-cells and various organs has sparked much interest. SerpinB1 emerged as a novel hepatokine inducing β-cell proliferation. However, its role in type-2-DM (T2DM) patients has not been adequately studied. This study was designed to investigate its circulating levels in subjects with/without T2DM, and to study its association with β-cell function, as well as various glycemic-control and lipid-profile parameters. Anthropometric data and biochemical markers including fasting plasma glucose (FPG), HbA1C % and lipid profile parameters were measured in 55 T2DM patients, as well as 30 healthy nondiabetic subjects. Serum …

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, …

A Novel Serpinb1 Single-Nucleotide Polymorphism Associated With Glycemic Control And Β-Cell Function In Egyptian Type 2 Diabetic Patients, Dina H. Kassem, Aya Adel, Ghada H. Sayed, Mohamed M. Kamal

Pharmacy

Aims: Serine protease inhibitor B1 (SerpinB1) is a neutrophil elastase inhibitor that has been proved to be associated with type 2 diabetes mellitus and pancreatic β-cell proliferation. In this study, we investigated 2 SERPINB1 SNPs, rs114597282 and rs15286, regarding their association with diabetes risk and various anthropometric and biochemical parameters in Egyptian type 2 diabetic patients.

Materials and Methods: A total of 160 subjects (62 control and 98 type 2 diabetic patients) participated in this study. Various anthropometric and biochemical parameters were assessed. Genotyping assay for the two SNPs was done using TaqMan genotyping assays. The association of rs15286 variants …

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 …

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, …

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,

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 …

Ligands Of Therapeutic Utility For The Liver X Receptors., Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar

Faculty and Staff Publications

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. …

Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …

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 …

Identification Of Plant Extracts That Inhibit The Formation Of Diabetes-Linked Iapp Amyloid, Ana Lucia Fuentes, Kathleen Hennessy, Jacob Pascual, Nicole Pepe, In Wang, Cynthia Chaggan, Jessica Martinez, Evelyn Rivera, Paola Cota, Christina Cunha, Luiza A. Nogaj, David A. Moffet

Chemistry and Biochemistry Faculty Works

The extracts of 27 vegetables, spices and herbs were screened for their functional ability to inhibit the aggregation of islet amyloid polypeptide (IAPP, amylin) into toxic amyloid aggregates. The aggregation of IAPP has been directly linked to the death of pancreatic β-islet cells in type 2 diabetes. Inhibiting the aggregation of IAPP is believed to have the potential to slow, if not prevent entirely, the progression of this disease. As vegetables, spices and herbs are known to possess many different positive health effects, the extracts of 27 plants (abundant within the United States and spanning several plant families) were screened …

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 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 …

Nonenzymatic Glycosylation Of Erythrocyte Membrane Proteins. Relevance To Diabetes, J A. Miller, Ellen M. Gravallese, H F. Bunn

Ellen M. Gravallese

Nonenzymatic glycosylation of proteins of the erythrocyte membrane was determined by incubating erythrocyte ghosts with [3H]borohydride. The incorporation of tritium into protein provides a reliable assay of ketoamine linkages. The membrane proteins from 18 patients with diabetes incorporated twice as much radioactivity as membrane proteins from normal erythrocytes. After acid hydrolysis, amino acid analysis showed that the majority of radioactivity was localized to glucosyllysine. Autoradiograms showed that all of the major proteins of the erythrocyte membrane, separated by electrophoresis on sodium dodecyl sulfate gels, contained ketoamine linkages. No protein bands in either normal or diabetic erythrocytes showed significant preferential labeling. …

Inhibition Of Toxic Iapp Amyloid By Extracts Of Common Fruits, David A. Moffet, Pei-Yu Kao, Evangeline Green, Catalina Pereirab, Shauna Ekimura, Dennis Juarez, Travis Whyte, Taylor Arhar, Bianca Malaspina, Luiza A. Nogaj

Chemistry and Biochemistry Faculty Works

The aggregation of the 37-amino acid polypeptide islet amyloid polypeptide (IAPP, amylin), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of pancreatic β-islet cells in type 2 diabetes. It is believed that inhibiting the aggregation of IAPP may slow down, if not prevent entirely, the progression of this disease. Extracts of thirteen different common fruits were analyzed for their ability to prevent the aggregation of amyloidogenic IAPP. Thioflavin T binding, immuno-detection and circular dichroism assays were performed to test the in vitro inhibitory potential of each extract. Atomic force microscopy was …

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 …

Identification Of Disufide Bond Formation Between Mitoneet And Glutamate Dehydrogenase 1, Morgan E. Roberts, Jacquelyn P. Crail, Megan M. Laffoon, William G. Fernandez, Michael A. Menze, Mary E. Konkle

Michael Menze

MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. Proteomic analysis identified the specific cysteine residues that participate in the disulfide bond. This is the first report that effectively links mitoNEET to activation of the insulin regulator GDH1.

Identification Of Disufide Bond Formation Between Mitoneet And Glutamate Dehydrogenase 1, Morgan E. Roberts, Jacquelyn P. Crail, Megan M. Laffoon, William G. Fernandez, Michael A. Menze, Mary E. Konkle

Faculty Research & Creative Activity

MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. Proteomic analysis identified the specific cysteine residues that participate in the disulfide bond. This is the first report that effectively links mitoNEET to activation of the insulin regulator GDH1.

Identification Of Disulfide Bond Formation Between Mitoneet And Glutamate Dehydrogenase 1, Morgan E. Roberts, Jacquelyn P. Crail, Megan M. Laffoon, William G. Fernandez, Michael A. Menze, Mary E. Konkle

Faculty Research & Creative Activity

MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. Proteomic analysis identified the specific cysteine residues that participate in the disulfide bond. This is the first report that effectively links mitoNEET to activation of the insulin regulator GDH1.

Identification Of Disufide Bond Formation Between Mitoneet And Glutamate Dehydrogenase 1., Morgan Roberts, Jacquelyn Crail, Megan Laffoon, William Fernandez, Michael Menze, Mary Konkle

Faculty Scholarship

MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. Proteomic analysis identified the specific cysteine residues that participate in the disulfide bond. This is the first report that effectively links mitoNEET to activation of the insulin regulator GDH1.

Improvement Of Functional Bioactivity In Pear:Blackberry Synergies With Lactic Acid Fermentation For Type 2 Diabetes And Hypertension Management, Nicholas W. Pucel

Masters Theses 1911 - February 2014

Type II diabetes mellitus (T2DM) is a chronic disease that has a worldwide prevalence which is expected to rise dramatically over the course of the next thirty years. The disease has reached pandemic stages of development in many cultures, most notably in developing countries, followed somewhat closely by developed countries with access to an overabundance of refined carbohydrates and fat (refined oils). T2DM is a condition that can be prevented or managed, but not cured; therefore a method of stymieing the development of this disease is paramount to halting its progressively increasing morbidity. In this study, bartlett pear and kiowa …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

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 …