Pharmacology, Toxicology and Environmental Health Commons^™

Microplastic Exposure Alters Tubulin Leading To Alterations In Insulin Secretion By Pancreatic Beta Cells, Anakaren Garcia

Honors Program Theses and Research Projects

Abstract

Diabetes mellitus is a metabolic disorder characterized by elevated blood glucose levels due to impaired insulin secretion or diminished cellular response to insulin (resistance). Pancreatic β-cells depend on a well-organized cytoskeleton, particularly microtubules composed of α- and β-tubulin heterodimers, to transport insulin granules to the plasma membrane during glucose-stimulated insulin secretion (GSIS). Disruption of microtubule organization can impair granule trafficking and reduce insulin release. However, emerging environmental toxicants such as microplastics that interfere with β-cell cytoskeletal function remains largely unexplored.

Microplastics (MPs) are small plastic particles (< 5 mm) that have become widespread environmental contaminants and can enter biological systems. Previous studies have shown that MPs can induce cellular stress and protein misfolding, but their effects on microtubules in pancreatic β-cells are not well characterized. This study investigates whether exposure to fluorescent polystyrene microplastics alters microtubule organization and insulin secretion in βTC-6 cells.

βTC-6 cells were treated with 10 µg/mL of fluorescent polystyrene microplastics for …

Streptozotocin-Induced Diabetes Increases Kidney Toxicity In Rats Exposed To Ochratoxin A, Belkys Gonzalez

Theses and Dissertations

Due to the rising occurrence of diabetes in the population and the prevalence of OTA exposure via ingestion of contaminated foodstuffs, there is a need to assess the possible renal interaction of a diabetic disease state in concurrence with OTA exposure. Sprague Dawley rats were treated with streptozotocin to induce experimental diabetes and then orally exposed to 0.5 mg/kg body weight OTA once a day for 21 days. Renal biomarkers and light microscopy were evaluated to assess the interaction between diabetic nephropathy and OTA exposure. LLC-PK1 proximal tubule cells were used as an in vitro model to assess the potential …

Gpr75 Deficiency Attenuates High Fat Diet-Driven Obesity And Glucose Intolerance, Sakib Hossain

NYMC Student Theses and Dissertations

Recently, a collaboration between Regeneron Pharmaceuticals and the Schwartzman-Garcia labs at New York Medical College published an exome sequencing study of individuals across the United Kingdom, United States, and Mexico which concluded that individuals possessing non-functioning, truncated mutations to the orphan g protein coupled receptor (GPCR), GPR75, had lower BMI and 54% reduced likelihood of obesity. The present study was undertaken to fully characterize the metabolic phenotype of Gpr75 deficient mice when fed a high fat diet (HFD) and explore potential mechanisms by which GPR75 activation links to increased adiposity and decreased glucose tolerance. After 14 weeks of HFD-feeding we …

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, …

Edible Mushrooms: An Emerging Therapeutic Of Diabetes, Nilanjan Chakraborty, Anuron Banerjee, Sudeshna Nandi, Swagata Sarkar, Krishnendu Acharya

The Thai Journal of Pharmaceutical Sciences

Diabetes is the third most customary non-infectious disease occurring worldwide and leads to untimely disability and mortality. This metabolic disorder is characterized by impaired insulin secretions and high blood glucose levels. Among others, type 2 diabetes is the most common. Various chemical and biochemical hypoglycemic drugs are utilized to control and treat hyperglycemia but required further interventions to reduce their toxicity and side effects on the users. Edible mushrooms have been employed from ancient times to heal many diseases as it composed of anti-oxidant, alkaloids, fibers, triterpenoids, and other phytochemicals. The bioactive secondary metabolites of mushrooms can improve insulin resistance …

A Review Of Covid-19 In Relation To Metabolic Syndrome: Obesity, Hypertension, Diabetes, And Dyslipidemia, Elias Makhoul, Joseph L. Aklinski, Jesse Miller, Cara Leonard, Sean Backer, Payal Kahar, Mayur S. Parmar, Deepesh Khanna

HPD Articles

Although severe cases and mortality of coronavirus disease 2019 (COVID-19) are proportionally infrequent, these cases are strongly linked to patients with conditions of metabolic syndrome (obesity, hypertension, diabetes, and dyslipidemia). However, the pathophysiology of COVID-19 in relation to metabolic syndrome is not well understood. Thus, the goal of this secondary literature review was to examine the relationship between severe acute respiratory syndrome (SARS-CoV-2) infection and the individual conditions of metabolic syndrome. The objective of this secondary literature review was achieved by examining primary studies, case studies, and other secondary studies, to obtain a comprehensive perspective of theories and observations of …

Body Mass Index (Bmi): A Screening Tool Analysis, Deepesh Khanna, Cadynce Peltzer, Payal Kahar, Mayur S. Parmar

HPD Articles

Body mass index (BMI), a measurement based on a person's height and weight, allows the classification of individuals into categories such as obese or overweight. With these classifications, we can assess risk for hypertension, diabetes, cancer, hypercholesterolemia, and other chronic diseases. Furthermore, childhood BMI serves as a prediction method for health and disease later in life. Along with BMI, researchers also study waist circumference and waist-to-hip ratio in correlation with the above-mentioned chronic illnesses. This brief review explores the associations between body mass index, waist circumference, and the waist-hip ratio as measurements and their capability as predictors for persistent conditions …

Small G- Protein Regulators Of Islet Beta Cell Function, Suhadinie Sameera Gamage

Wayne State University Dissertations

Defects in insulin secretion from pancreatic islet beta- cells leads to long term complications such as type 2 diabetes mellitus. The mechanism and regulation of glucose stimulated insulin secretion (GSIS) as well as factors contributing to pancreatic islet beta-cell demise are yet poorly understood. Previous work from our laboratory demonstrated that Ras-related C3 botulinum toxin substrate 1 (Rac1), a small G- protein is involved in GSIS as well as in culminating dysfunction under metabolic stress. Cycling of Rac1 between its inactive and active form is considered a vital event in glucose stimulated insulin secretion. This conversion is made possible by …

The Effect Of Pioglitazone On Phosphoproteome And Interactome Of Protein Phosphatase 2a In Primary Human Skeletal Muscle Cells, Lana Alghanem

Wayne State University Dissertations

Skeletal muscle insulin resistance is one of the main contributors to Type 2 Diabetes (T2D), which is a chronic disease affecting 37.3 million people in United States (US), with an estimated annual cost exceeding $300 billion in the US. T2D is being treated with a variety of medications, including Pioglitazone (PIO), a potent insulin sensitizer for skeletal muscle. PIO is a synthetic ligand for the peroxisome proliferator-activated receptor (PPAR-γ), nuclear receptors regulating the expression of many genes involved in lipid and glucose metabolism. To date, the molecular action of PIO that sensitizes muscle to insulin is incompletely understood. Protein phosphorylation …

Analysis Of Hba1c, Medication Compliance, Income Subsidies, And Comorbidity In Medicare Type 2 Diabetics, Robert E. Lazarchik

Walden Dissertations and Doctoral Studies

Diabetes is one of America’s leading chronic diseases with comorbidities contributing to lower health statuses and increased health care costs. While it is known that lowering HbA1c reduces the deleterious effects of diabetes, the capability to identify people with diabetes at risk for uncontrolled HbA1c levels or developing comorbidities based on the compliance rates for different oral antihyperglycemic medication classes (OAMCs) and financial assistance programs does not yet exist. These quantitative longitudinal retrospective studies examined the association between medication compliance, using Proportion of Days Covered (PDC), by OAMC and Medicare financial aid programs, on predicting HbA1c levels and comorbidities in …

Lemongrass (Cymbopogon Citratus) Ethanolic Extract Exhibited Activities That Inhibit -Glucosidase Enzymes And Postprandial Blood Glucose Elevation, Maria Dewi Puspitasari Tirtaningtyas Gunawan Puteri, Felicia Melissa Tjiptadi, Phebe Hendra, Filiana Santoso, Zalinar Udin, Nina Artanti, Florence Ignatia Florence Ignatia

Makara Journal of Science

Lemongrass is a common ingredient in Indonesian traditional herbal medicine that potently inhibits carbohydrate hydrolysis. In this study, the in vitro α-glucosidase inhibitory (AGI) activity of lemongrass was compared with its in vivo activity to retard postprandial blood glucose elevation, and the bioactive compounds responsible for these activities were observed. Both water and ethanolic extracts of lemongrass (WLG and ELG, respectively) were tested in vitro for its inhibition of the sucrose and maltose hydrolyzing activities of rat intestinal glucosidase. ELG was observed to exert higher inhibitory activities (Sucrase IC₅₀ = 8.74 mg/mL; Maltase IC₅₀ = 18.93 mg/mL) than …

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

Honors Theses

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

Intra-Ocular Vascular Endothelial Growth Factor Inhibiting Agents: Indications, Efficacy, And Alternatives, Rena Shilian

The Science Journal of the Lander College of Arts and Sciences

One of the most revealing parts of the human body is the eye. In fact, systemic conditions and diseases are commonly manifested in the eye and display pathology that reflect disorders. An example of a chorioretinal vascular condition that can present itself in the eye is diabetes mellitus, which if left uncontrolled can damage the eyes and a person’s vision. Age related macular degeneration is specific to the eye, potentially leading to irreversible loss of central vision. Intravitreal injections containing vascular endothelial growth factor inhibiting agents appear to be the leading lines of defense against diabetic retinopathy and macular degeneration …

Are Health Problems In Adulthood Linked To Our Experiences In The Womb? An Epigenetic Approach, Simone Tendler

The Science Journal of the Lander College of Arts and Sciences

The origins of adult disease have been a prime topic for research, as deciphering causes can lead to strategies for preventions and cures. There has been recent intrigue focused on the environment in the womb. Records from England and Wales in 1911 show that those who suffered from cardiovascular disease were geographically correlated with regions high in infant mortality in the past, seventy years before the study. When looking into the cause of the neonatal death rates, low birth weight, poor maternal health, and high maternal death rates during childbirth were clearly associated. Barker inferred that there is much happening …

Impact Of Physical Activity On Type 2 Diabetes Mellitus, Marshall Schwartz

The Science Journal of the Lander College of Arts and Sciences

Type 2 diabetes mellites has become an increasingly prevalent worldwide epidemic. The tremendous economic burden, coupled with the numerous secondary risks associated with the disease, have encouraged researchers to search for causes as well as treatment methods. This research paper focuses on the effect of physical activity as a preventative measure for those at risk for diabetes and as a treatment method for those already diagnosed with the disease. The articles collected included meta-analysis, randomized controlled trials, cohort studies, surveys, etc. The studies that were analyzed have indicated an inverse relationship between physical activity and type 2 diabetes. Since there …

Novel Calcium-Related Targets Of Insulin In Hippocampal Neurons, Shaniya Maimaiti, Hilaree N. Frazier, Katie L. Anderson, Adam O. Ghoweri, Lawrence D. Brewer, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Both insulin signaling disruption and Ca²⁺ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca²⁺-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca²⁺-dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in …

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 …

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 …

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 …

Drug-Induced Nutrient Depletion, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Mechanisms Of Pancreatic Beta Cell Dysfunction In Diabetes, Vaibhav Sidarala

Wayne State University Dissertations

Diabetes is a serious medical condition characterized by decreased insulin secretion from pancreatic β-cells and decreased insulin sensitivity in the peripheral tissues, resulting in elevated levels of blood glucose. According to the International Diabetes Federation, about 387 million cases have been reported worldwide in the year 2013 and it is estimated that about 500 million people would be affected by 2050. Type 2 diabetes, which accounts for about 90% of the total number of cases, is caused by decreased insulin sensitivity in the peripheral tissues and decreased glucose-stimulated insulin secretion from the pancreatic β-cells. The underlying mechanisms involved in β-cell …

Sleep Duration And Diabetes In An Adult Population Of Rural Upstate New York, Tarak Shrestha

Legacy Theses & Dissertations (2009 - 2024)

Introduction: Within the past five decades, there has been a rapid increase in the number of diabetic cases in the US. The number of diabetic cases increased from 1.5 million in 1959 to 25.8 million in 2011. Around the same time period, the average sleep duration per night decreased from 8 hours to 6.9 hours.

The Modulatory Role Of Circulating Microvesicles In Endothelial Progenitor Cell Function Is Altered In T2dm, Hala Mustafa Ammar

Browse all Theses and Dissertations

Circulating microvesicles (cMVs) are the extracellular MVs released from the cells in the blood and on the vascular wall. Our previous study demonstrates that cMVs of diabetic mouse are detrimental to endothelial progenitor cells (EPCs), which are known to be very important for maintaining normal endothelial function and structure. In this study, we compared the levels of circulating EPCs and EPC-derived MVs (EPC-MVs) in diabetic and healthy subjects. Also, the migration ability, apoptosis rate and reactive oxygen species (ROS) production of EPCs cultured from diabetic and healthy subjects were determined. More importantly, we evaluated whether cMVs from healthy subjects (ch-MVs) …

Increased Urinary Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Type 2 Diabetic Patients, Sridevi Gutta

Browse all Theses and Dissertations

Chronic Kidney Disease (CKD) has reached epidemic proportions affecting more than 20 million adults in the US. CKD is routinely diagnosed and defined as reduced glomerular filtration rate (GFR), increased urinary albumin creatinine ratio (UACR) or both. Diabetes, hypertension and obesity share a major part in causing CKD. Angiotensin (1-7) (Ang (1-7)) is a vasodilator that plays an important renoprotective role in the renin angiotensin system, counteracting the vasoconstrictor and proliferative effects of Ang II. ACE2 and NEP which form Ang (1-7) by degrading Ang II and Ang I, respectively. A Disintegrin and Metalloproteinase (ADAM) 17, which is responsible for …

Effects Of Anti-Inflammatory Foods On Hyperglycemia In Type-1 Diabetics, Primrose Martin, Michelle Chino

McNair Poster Presentations

Based on a case study administered by Dr. Charlotte Gerson, an IDDM patient referred to as R.H. reversed hyperglycemic symptoms within ten weeks while adhering to a diet of mainly vegetables and some low-glycemic index fruits. R.H. also ingested mineral supplements and underwent multiple coffee enemas each day (Gerson & Bishop, 2007, p. 56). This self-study hypothesizes that diet alone has a positive correlation coefficient with hyperglycemic blood glucose levels in type-1 diabetics (IDDM). Conducting this self-study contributes information to the limited research and database of alternative methods for managing IDDM hyperglycemia, and provides candid documentation of the effects that …

Isolation And Characterization Of Natural Alpha-Glucosidase Inhibitors From Antioxidant Rich Red Wine Grapes (Vitis Vinifera), Hoda Chaouki Kadouh

Wayne State University Dissertations

Background: Diabetes is currently a global public health problem affecting people at all ages. Dietary antioxidants have been associated with a reduced risk of type 2 diabetes. Grape pomace contains considerable amounts of polyphenols and it has been reported to exhibit an inhibitory activity against alpha- glucosidases. Alpha-glucosidases, in turn, play a major role in controlling starch digestion and therefore postprandial blood glucose, a target for diabetes management.

Objective: This study aims to investigate the anti-diabetes potential of a selection of six grape pomaces and prepare and purify active components in the active variety that specifically inhibit intestinal alpha-glucosidases. The …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Role Of Hyperglycemia And Aldosterone On Renal Ace2 And Albuminuria In Db/Db Mice, Harshita Chodavarapu

Browse all Theses and Dissertations

Diabetic nephropathy (DN) is one of the microvascular complications of type II diabetes and a leading cause for the development of end stage renal disease. Renin angiotensin system (RAS) plays a pivotal role in the development and progression of diabetic nephropathy. Hyperglycemia activates RAS and increases tissue and circulating levels of angiotensin II (Ang II) and aldosterone. A new component of RAS, angiotensin converting enzyme 2 (ACE2), has been shown to be renoprotective in early stages of diabetes. The aim of this study is to test the hypothesis that strict glycemic control using rosiglitazone or treatment with mineralocorticoid receptor (MR) …