Chemicals and Drugs Commons^™

Overview Of Glp-1ra Medications, Thomas A.F. Cordaro Pharmd, Sumaiya A. Difaa Pharmd, Amel J. Basil Pharmd

Transformative Medicine

GLP-1 is an incretin hormone that is naturally produced in the body that regulates blood glucose and appetite. The first GLP-1RA that was FDA approved, exenatide, in 2005, originated from the Gila monster and beaded lizard, via the discovery of the exendin-4 peptide. GLP-1RAs function by mimicking endogenous GLP-1 incretin hormone, leading to an increase in glucose-dependent insulin release from beta-cells of the pancreas, decrease in glucagon release, delayed gastric emptying, and satiety. Due to the benefits seen from initiating GLP-1RAs in the market, it sparked interest in numerous studies which proved that certain GLP-1RAs can provide cardiorenal protection. The …

Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler

MUSC Theses and Dissertations

Diabetes Mellitus (DM) affects 13.9% of men and 14.3% of women worldwide, a total of approximately 828 million people. Patients with diabetes are at risk of several complications including diabetic nephropathy (DN) and metabolic-associated steatohepatitis (MASH). These diseases eventually lead to end stage kidney disease (ESKD) and liver failure requiring dialysis and organ transplantation. In addition, diabetes exacerbates disease severity of autosomal dominant polycystic kidney disease (ADPKD), the most common potentially lethal genetic disease to affect humans with a prevalence of 1 in 500-1000. Therefore, a therapeutic approach that can attenuate organ damage and restore function in patients with DM, …

The Effect Of Glp-1 Receptor Agonists On Reoperation Following Anterior Cervical Discectomy And Fusion, Nicholas C. Bank, Daniel Whittingslow, Sam Duggan, Joshua L. Morningstar, Douglas S. Weinberg

Student Papers, Posters & Projects

BACKGROUND: Pseudarthrosis remains a significant complication of ACDF, contributing to patient morbidity and increased healthcare costs. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for diabetes and obesity, have been shown to reduced odds of pseudoarthrosis after ACDF. However, it remains unclear whether these reductions meaningfully translate to reduced odds of subsequent cervical surgery.

METHODS: The TriNetX United States Collaborative Network was queried for patients who underwent single- or multi-level ACDF between 2013-2023. Patients with perioperative GLP-1RA use and propensity-score-matched controls without GLP-1RA use were compared for subsequent rates of pseudoarthrosis and cervical reoperation at 6-, 12-, and 24-month intervals. Odds …

The Use Of Glp-1 Agonists In Alcohol Use Disorder And Reducing Alcohol Consumption: A Scoping Review, Alec Birnbaum, Yashas Sattur, Akash Patel

Rowan-Virtua Research Day

Alcohol use disorder (AUD) reigns as one of the most pressing issues in the United States with high rates of complications, morbidity, and mortality. Recent studies have exhibited the potential for Glucagon-Like Peptide-1 (GLP-1) agonists to decrease alcohol cravings or alcohol-related adverse events through human and animal studies via reward and satiety signaling pathways. To investigate the ability of GLP-1 agonists to decrease alcohol use, alcohol cravings, and alcohol-related adverse events, this study conducted a scoping review of the current literature to uncover the potential benefit of GLP-1 agonists in patients with AUD. A systematic search across 6 databases was …

Efficacy Of Glucagon-Like Peptide-1 Receptor Agonists For Prevention Of Stroke Among Patients With And Without Diabetes: A Meta-Analysis With The Select And Flow Trails, Asmita Gera, Fakhar Latif, Vamsikalayan Borra, Sidra Naz, Vivek Mittal, Fathima Shehnaz Ayoobkhan, Tushar Kumar, Zarghoona Wajid, Novonil Deb, Tanisha Prasad

School of Medicine Publications

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, its efficacy on cerebrovascular events is yet to be well established among diabetic and non diabetic patients.

Objective

We sought to evaluate the efficacy of GLP-1 RAs on stroke risk among its different types in patients with and without Diabetes.

Methods

We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until 15th July 2024, without any language restrictions. Odds ratios (OR) and 95 % …

From Trial To The Prescription Pad: Quality Improvement Of Sglt-2 Inhibitor Prescription Prevalence For Patients With Diabetes And Heart Failure, Grace Fawcett, Victoria Blaisdell, Riley King, William Hannah, Eric Shaw

South Atlantic Division GME Research Day 2025

No abstract provided.

Transcription And Post-Translational Mechanisms: Dual Regulation Of Adiponectin-Mediated Occludin Expression In Diabetes, Yanru Duan, Demin Liu, Huahui Yu, Shihan Zhang, Yihua Xia, Zhiyong Du, Yanwen Qin, Yajing Wang, Xin-Liang Ma, Huirong Liu, Yunhui Du

Department of Emergency Medicine Faculty Papers

BACKGROUND: Occludin, a crucial component of tight junctions, has emerged as a promising biomarker for the diagnosis of acute ischemic disease, highlighting its significant potential in clinical applications. In the diabetes, Occludin serves as a downstream target gene intricately regulated by the adiponectin (APN) signaling pathway. However, the specific mechanism by which adiponectin regulates Occludin expression remains unclear.

METHODS AND RESULTS: Endothelial-specific Ocln knockdown reduced APN-mediated blood flow recovery after femoral artery ligation and nullified APN's protection against high-fat diet (HFD)-triggered apoptosis and angiogenesis inhibition in vivo. Mechanically, we have meticulously elucidated APN's regulatory role in Occludin expression through a …

Exploring The Metabolic And Mitogenic Potential Of A Hyper-Stable Variant Of Fgf1, Emma Starr, Oshadi Edirisinghe, Thallapuranam Krishnaswamy Suresh Kumar

Inquiry: The University of Arkansas Undergraduate Research Journal

Fibroblast growth factors (FGFs) are a family of 22 human cytokines involved in critical cellular processes, such as proliferation, differentiation, metabolism, angiogenesis, tumor metastasis, and wound healing. Among these, fibroblast growth factor 1 (FGF1) possesses a powerful mitogenic potential as it can nonspecifically bind to all four FGF receptors. However, the therapeutic applications of FGF1 are hindered by its inherent thermal and proteolytic instability, especially at physiological temperatures. This is believed to be attributed to the heparin-binding pocket at the C-terminus, which contains numerous positively charged residues that repel each other. To combat this instability, FGF1 binds to a negatively …

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Studies & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Examining The Oxidative Stress Effects In Rats Exposed To 2-Aminoanthracene In Utero And High Fat Diet Three Months After, Brianna A. Lanoix

Honors College Theses

Polycyclic aromatic hydrocarbons are organic compounds that are created synthetically or found in partially burned oil, gasoline, and coal. 2-aminoanthracene (2AA) is a common example of a PAH and can affect lipid and carbohydrate metabolism and resulting in inflammatory problems and oxidative stress. The objective of the research project is to investigate oxidative stress in relation to diabetes in rats exposed to 2AA in utero and a high fat diet later in life. Pregnant dams were separated into treatment groups based on their dosages of 2AA; 0 mg/kg (control), 50 mg/kg (low), 100 mg/kg (high). During the gestation -postpartum period, …

The Glycemic, Cholesterol, And Weight Effects Of L-Carnitine In Diabetes: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Jennifer Ko, Eva Y. Wong, Huyentran N. Tran, Rebecca J.C. Tran, Diana X. Cao

Pharmacy Faculty Articles and Research

Introduction

L-carnitine possibly impacts insulin sensitivity and glucose metabolism. However, its therapeutic role in diabetes is poorly understood.

Methods

A systematic review and meta-analysis were conducted using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through June 30, 2021. Included studies evaluated the use of L-carnitine in diabetes on fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), weight, or body mass index (BMI). Weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects model.

Results

Seventeen studies …

The Role Of Age Ligand And Rap1a In Myofibroblast Signaling Cascade In Type 2 Diabetes Mellitus-Induced Cardiomyopathic Conditions, Camilla Puglia

Honors Theses

Diabetes is one of the leading causes of death in the United States, taking more than 90,000 lives annually. Type 2 diabetes mellitus-induced cardiac fibrosis is a common condition seen in diabetic patients. The AGE/RAGE signaling cascade has been strongly associated with this supposed cardiac fibrosis along with hyperactive myofibroblasts which excessively remodel extracellular matrix tissue, leading to damaged and enlarged heart muscle tissue. In diabetic patients, Advanced Glycation End Products (AGEs) are produced in abundance and accumulate in the extracellular matrix of heart tissue. To investigate the role of of the AGE ligand on fibroblast behavior, increasing amounts of …

Sex Differences In The Association Of Sibship Size And Position In Sibship With Lipid Profile During Adolescence: A Cross-Sectional Study, Ali H. Ziyab, Mohammad Almari, Anwar Mohammad, Abdullah Al-Taiar, Wilfried Karmaus

Community & Environmental Health Faculty Publications

Background. Epidemiologic studies have reported associations of sibship size and position of the child in the sibship with multiple health outcomes, including adiposity and diabetes. However, little is known about sibling effects on lipids. Hence, this study sought to evaluate associations of the number of total, older, and younger siblings with lipid profile among adolescents. Methods. In a cross-sectional study among high school students aged 14 to 19 years, lipid levels were measured in capillary blood. Parents reported the number of siblings (total, older, and younger). Geometric means of lipids were calculated, and linear regression was used to estimate the …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

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, …

The Interconnectivity Of Parkinson's Disease And Type Two Diabetes Mellitus, Erica Olfson

Honors Scholars Collaborative Projects

This thesis is about the biochemical connection between Parkinson's disease and Type II Diabetes Mellitus.

Exosomes From Mirna-126-Modified Endothelial Progenitor Cells Alleviate Brain Injury And Promote Functional Recovery After Stroke, Jinju Wang, Shuzhen Chen, Wenfeng Zhang, Yanfang Chen, Ji Chen Bihl

Pharmacology and Toxicology Faculty Publications

Aims: We previously showed that the protective effects of endothelial progenitor cells (EPCs)-released exosomes (EPC-EXs) on endothelium in diabetes. However, whether EPC-EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC-EXs on diabetic stroke mice and tested whether miR-126 enriched EPC-EXs (EPC-EXs miR126 ) have enhanced efficacy. Methods: The db/db mice subjected to ischemic stroke were intravenously administrated with EPC-EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase-3, miR-126, and VEGFR2 were measured on day 2 …

Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Reactive a-dicarbonyls (a-DC’s), such as methylglyoxal (MGO), are unavoidable metabolites generated during glycolysis that accumulate with age and have been linked with chronic age-related metabolic diseases such as Diabetes Mellitus. Diabetes Mellitus is generally characterized by peripheral neuropathy and sustained hyperglycemia. Chronic hyperglycemia leads to an increase in glycolysis and a downstream increase in reactive a-DC’s. The human body has a natural method of detoxifying these a-DC’s. Glycolytic cells have enzymes which can detoxify a-DC’s, but if overwhelmed, a-DC’s can accumulate and react non-enzymatically with proteins, lipids and DNA to yield a group of molecules called advanced glycation end-products (AGEs). …

Observing Growth Effects Of Pigment Epithelium-Derived Factor On Human Retinal Pericytes In Vitro, Anjalee Choudhury, Andrew Tsin, Zachary Perez, Fransisco Elisarraras

School of Medicine Publications

The purpose of this study is to investigate and determine the role of PEDF in the pathogenesis of diabetic retinopathy as induced by advanced glycation end-products (AGEs). Human retinal pericytes were isolated from donors and will be measured for cell proliferation under the influence of PEDF both in the presence and absence of AGEs. Expected outcomes involve both the maintenance and increased survival of HRPs after treatment with PEDF under stimulated hyperglycemic conditions.

Prevention Of Renal Apob Retention Is Protective Against Diabetic Nephropathy: Role Of Tgf-Β Inhibition, Patricia G. Wilson, Joel C. Thompson, Meghan S. Yoder, Richard Charnigo, Lisa R. Tannock

Internal Medicine Faculty Publications

Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr^−/− mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect …

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 …

Succination Impairs Protein Folding And Promotes Chop Stability In The Adipocyte During Diabetes, Allison Manuel

Theses and Dissertations

Type 2 diabetes mellitus has been diagnosed in ~21 million people in the United States and is closely correlated with obesity, prompting the need for a detailed understanding of adipocyte metabolism in the development of diabetes. The intake of excess nutrients surpasses the energy requirements of the cell and leads to increased mitochondrial stress in the adipocyte. We have shown that this is associated with increased levels of the mitochondrial metabolite fumarate. Fumarate can react with cysteine thiol groups to form the chemical modification S-(2-succino)cysteine (2SC), also termed protein succination. Succination is significantly increased in the adipose tissue of type …

Drug-Induced Nutrient Depletion, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

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 …

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 …

Regulation Of Ghrelin: A Possible Treatment Option For Obesity And Diabetes, Sarah Picciotto

The Science Journal of the Lander College of Arts and Sciences

Obesity is a mounting problem in America today. One major concern about obesity is that it is a risk factor for type 2 diabetes, a disease that impairs insulin sensitivity and secretion. This interferes with blood glucose levels and can cause hyperglycemia, which is when there is too much circulating glucose in the blood. Ghrelin, an amino acid peptide responsible for appetite stimulation and energy balance, plays a direct role in insulin secretion and glucose metabolism. In many experiments, elevated ghrelin levels are associated with decreased insulin secretion from pancreatic islet cells. Although ghrelin concentration is decreased in obese individuals …

Effects Of Fatty Acids And Glycation On Drug Interactions With Human Serum Albumin, Jeanethe Anguizola, Sara B. G. Basiaga, David S. Hage

David Hage Publications

The presence of elevated glucose concentrations in diabetes is a metabolic change that leads to an increase in the amount of non-enzymatic glycation that occurs for serum proteins. One protein that is affected by this process is the main serum protein, human serum albumin (HSA), which is also an important carrier agent for many drugs and fatty acids in the circulatory system. Sulfonylurea drugs, used to treat type 2 diabetes, are known to have significant binding to HSA. This study employed ultrafiltration and high-performance affinity chromatography to examine the effects of HSA glycation on the interactions of several sulfonylurea drugs …

Diabetic Db/Db Mice Exhibit Central Nervous System And Peripheral Molecular Alterations As Seen In Neurological Disorders., A. Ernst, Ajaykumar Narayan Sharma, Khalid M. Elased, P. C. Guest, H. Rahmoune, S. Bahn

Pharmacology and Toxicology Faculty Publications

The db/db mouse is a widely used preclinical model in diabetes research. Recent studies have shown that these mice also display aspects of psychosis and depression-like behaviors as seen in some psychiatric disorders. Here, we have performed multiplex immunoassay and liquid chromatography mass spectrometry profiling of the plasma and brain samples from db/db and control mice to identify altered pathways, which could be related to these behavioral abnormalities. This is the first study to carry out profiling of the brain proteome in this model. Plasma from the db/db mice had increased levels of leptin and insulin, decreased levels of peptide …