Physiology Commons^™

Dim Light At Night Worsens Cardiac Autonomic Dysregulation In Female Diabetic Mice, Abhilash Prabhat, Shrishti Naidu, Isabel G. Stumpf, Tanya S. Seward, Elizabeth A. Schroder, Brian P. Delisle

Physiology Faculty Publications

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. CAN is characterized by impaired cardiovascular autonomic control and is associated with increased mortality, especially among women with type 2 diabetes. Identifying environmental factors that exacerbate the CAN-associated phenotype may reveal modifiable strategies to reduce cardiovascular risk.

Nighttime light exposure is a novel cardiovascular risk factor. Among ∼90,000 individuals, greater nighttime light exposure correlated with increased atrial fibrillation and heart failure risk. Light at night disrupts sympathovagal balance and elevates nocturnal heart rate in humans. Dim light at night similarly disrupts autonomic regulation of heart rate in mice. We …

The Role Of Inflammatory Cytokines In The Bidirectional Relationship Between Periodontitis And Diabetes Mellitus, Andrew R. Witty

Oral Health

Periodontitis and type 2 diabetes mellitus are associated with each other in a bidirectional relationship. The mechanism by which diabetes affects periodontitis is understood to be due to the inflammatory effects of hyperglycemia (high blood glucose levels) and a hospitable environment for sugar-consuming bacteria. Periodontitis is known to be associated with higher levels of glycated hemoglobin (HbA_1c), a long-term measurement of blood glucose control, and treatment of periodontitis reduces HbA_1c. Inflammation caused by periodontitis induces insulin resistance (which leads to higher blood glucose levels), but due to the complex nature of inflammation it is difficult to …

Adipocyte-Derived Cchamide-1, Eiger, Growth-Blocking Peptide 3, And Unpaired 2 Regulate Drosophila Melanogaster Oogenesis, Chad Simmons, Isaiah Williams, Tancia Bradshaw, Alissa R. Armstrong

Faculty Publications

In addition to energy storage, adipose tissue communication to other organs plays a key role in regulating organismal physiology. While the link between adipose tissue dysfunction and pathophysiology, including diabetes, chronic inflammation, and infertility, is clear, the molecular mechanisms that underlie these associations have not been fully described. We use Drosophila melanogaster as a model to better understand how adipose tissue communicates to the ovary. In this study, we utilized D. melanogaster’s robust genetic toolkit to examine the role of five adipokines known to control larval growth during development, CCHamide-1, CCHamide-2, eiger, Growth-blocking peptide 3, and unpaired 2 in regulating …

The Anti-Diabetic Drug Metformin Disrupts Feeding And Sleeping Behaviors In Drosophila Melanogaster, Lucas Fitzgerald

The Cardinal Edge

Dimethylbiguanide, also known as metformin, is the single most prescribed oral treatment for non-insulin dependent diabetes mellitus, or type 2 diabetes, in western countries. The primary mechanism of action that metformin acts through is the activation of AMP kinase, an important regulator of energy homeostasis. While the anti-diabetic effects of metformin are well documented, its effects on feeding and sleeping behaviors are not well characterized. Using the model organism Drosophila melanogaster, the mean daily quantity of food consumed was measured and compared between groups treated with several dosages of metformin. Feeding interactions such as meal frequency and length were …

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …

Diabetes Screening Among Women With Polycystic Ovary Syndrome: A Descriptive Study Of Commercial Claims, 2011–2019, Jacklyn Vollmer, W. Jay Christian, Mary E. Lacy

UK CARES Faculty Publications

Background Polycystic ovary syndrome (PCOS) is a hormonal disorder that affects 6–12% of United States women of reproductive age. Because women with PCOS are at an increased risk of developing type 2 diabetes, clinical practice guidelines from a number of organizations (e.g. American Diabetes Association, American College of Obstetricians and Gynecologists, US Preventive Services Task Force) recommend that individuals with PCOS are routinely screened for diabetes. Guidelines further indicate that an oral glucose tolerance test (OGTT) should be used for diabetes screening in women with PCOS as opposed to an A1C or fasting plasma glucose test. The purpose of this …

Effects Of Exercise Or Metformin On Myokine Concentrations In Patients With Breast And Colorectal Cancer: A Phase Ii Multi-Centre Factorial Randomized Trial, Justin C. Brown, Guillaume Spielmann, Shengping Yang, Stephanie L.E. Compton, Lee W. Jones, Melinda L. Irwin, Jennifer A. Ligibel, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. Methods: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I–III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were …

The Delineation Of Platelet Pathology In Cardiometabolic Disease, Chi Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a multifactorial disease with many comorbidities leading to multiorgan dysfunction. Current studies point towards dysregulation of platelet signaling as a driver for increased risk of cardiovascular disease and stroke. The exact mechanisms remain elusive due to the complex interplay of factors involved, warranting the need to further understand how platelets are affected. Our preliminary data evaluating changes in platelet and coagulation parameters from bariatric patients showed that obesity did not affect platelet count or clotting time as demonstrated in INR values. However, female patients had increased bleeding events before surgery that were decreased after surgery. Due to limitations …

Effectiveness Of Intervention Studies Based On Diet And/Or Physical Activity In Treatment, Prevention, And Management Of Diabetes Among South Asians: A Systematic Review, Ishaan Arora

Theses and Dissertations

The purpose of this study was to describe diet and/or physical activity-based interventions and their control in cardiometabolic risk factors of diabetes for the South Asian (SA) population. A systematic review was conducted in accordance with the PRISMA guidelines. Seventeen randomized control trials meeting the inclusion criteria were included for analysis. Interventions with type-2 diabetic SA showed significant improvements in HbA1c% (4/5 studies), fasting blood glucose (3/4 studies), and postprandial glucose (2/2 studies). Interventions with at-risk/prediabetic and non-diabetic SA showed a modest change in overall outcomes, with significant change reported for post-prandial insulin (3/4 studies), BMI and weight (2/4 studies), …

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 …

Brown Adipose Tissue (Bat) Activation And Its Potential Utilization As A Treatment Option For Obesity And Diabetes, Darcie B. Schneider

Student Publications

Within the human body, there are two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is beneficial for insulation whereas BAT has thermogenic capacity. BAT activation increases energy consumption via heat generation. Increased energy expenditure is associated with improved glucose and lipid metabolism. Therefore, BAT activation research has primarily been aimed at its potential use in the treatment of obesity, diabetes, and other metabolic disorders. In this literature review, BAT's thermogenic mechanisms, techniques of activation, potential therapeutic targets, and future research topics are explored.

Sleep And Risk For Metabolic Syndrome, Hypertension, Diabetes And Obesity Among Community-Dwelling Older Adults, Philip Zendels, Trudy L. Moore-Harrison, Jane F. Gaultney

International Journal of Exercise Science

International Journal of Exercise Science 15(3): 88-102, 2022. Older adults often face a variety of health problems that are found less frequently in younger populations. Metabolic syndrome and other related diseases are common due to a variety of age and lifestyle factors. Sleep, often operationalized only as duration, quality, or apnea diagnosis, is associated with worse health outcomes across the lifespan. However, sleep is multi-faceted and may require a collection of measures in order to reflect this. This study examined a suite of self-reported sleep habits (risk for sleep apnea, night time duration, nap duration, quality, timing, and consistency of …

Fibroblast Growth Factor 19 Increases The Excitability Of Pre-Motor Glutamatergic Dorsal Vagal Complex Neurons From Hyperglycemic Mice, Jordan B. Wean, Bret N. Smith

Physiology Faculty Publications

Intracerebroventricular administration of the protein hormone fibroblast growth factor 19 (FGF19) to the hindbrain produces potent antidiabetic effects in hyperglycemic mice that are likely mediated through a vagal parasympathetic mechanism. FGF19 increases the synaptic excitability of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) from hyperglycemic, but not normoglycemic, mice but the source of this synaptic input is unknown. Neurons in the area postrema (AP) and nucleus tractus solitarius (NTS) express high levels of FGF receptors and exert glutamatergic control over the DMV. This study tested the hypothesis that FGF19 increases glutamate release in the DMV …

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 …

Serum Apolipoproteins And Apolipopprotein-Defined Lipoprotein Subclasses: A Hypothesis-Generation Prospective Study Of Cardiovascular Events In Type 1 Diabetes, Arpita Basu Phd, Ionut Bebu Phd, Alicia J. Jenkins Md, Julie A. Stoner Phd, Ying Zhang Md; Phd, Richard L. Klein Phd, Maria F. Lopes-Virella Md; Phd, W. Timothy Garvey Md, Matthew J. Budoff Md, Peter Alaupovic Phd, Timothy J. Lyons Md

Kinesiology and Nutrition Sciences Faculty Research

Apolipoproteins and apolipoprotein-defined lipoprotein subclasses have been associated with dyslipidemia and cardiovascular disease (CVD). Our main objective was to define associations of serum apolipoproteins and ADLS with any CVD and major atherosclerotic cardiovascular events (MACE) in a prospective study of T1D. Serum apolipoproteins and ADLS (14 biomarkers in total) were measured in sera (obtained 1997-2000) from a subset (n=465) of the Epidemiology of Diabetes Interventions and Complications (EDIC) cohort. Prospective associations of any CVD (myocardial infarction, stroke, confirmed angina, silent MI, revascularization, or congestive heart failure) and MACE (fatal or nonfatal myocardial infarction or stroke), over 5942 and 6180 patient-years …

Cardio-Metabolic Disease Risk Factors Among South Asian Labour Migrants To The Middle East: A Scoping Review And Policy Analysis, Shiva Raj Mishra, Saruna Ghimire, Chandni Joshi, Bishal Gyawali, Archana Shrestha, Dinesh Neupane, Sudesh Raj Sharma, Yashashwi Pokharel, Salim S. Virani

School of Public Health Faculty Research

This paper aims to explore the burgeoning burden of cardiovascular and metabolic disease (CMD) risk factors among South Asian labor migrants to the Middle East. We conducted a qualitative synthesis of literature using PubMed/Medline and grey literature searches, supplemented by a policy review of policies from the South Asian countries. We found a high burden of cardio-metabolic risk factors among the migrants as well as among the populations in the home and the host countries. For example, two studies reported the prevalence of diabetes mellitus (DM) ranging between 9 and 17% among South Asian migrants. Overweight and obesity were highly …

Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou

Theses and Dissertations--Pharmacology and Nutritional Sciences

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2^Luc mouse model (db/db-mPer2^Luc) that allows quantitatively measuring of mPER2 protein oscillation …

Oral Glucose Insulin Secretion Test For Identifying Patients With Insulin Resistance, David Kershner

Walden Dissertations and Doctoral Studies

Insulin resistance is an increasing public health issue with the current literature, suggesting reduced sensitivity of insulin leads to adult onset diabetes and associated downstream pathologies that reduce life expectancy. The main objectives of this study were to evaluate the ability of the Oral Glucose Insulin Secretion Test (OGIST) to identify insulin resistance and examine differences in the insulin sensitivity based on gender, age, and ethnicity. This study was supported by the insulin resistance theory which focuses on the reduced ability of insulin to bind to the cellular insulin receptor, reducing the sensitivity of insulin. The OGIST lab results of …

Methylglyoxal Requires Ac1 And Trpa1 To Produce Pain And Spinal Neuron Activation, Ryan B. Griggs, Don E. Laird, Renee R. Donahue, Weisi Fu, Bradley K. Taylor

Physiology Faculty Publications

Methylglyoxal (MG) is a metabolite of glucose that may contribute to peripheral neuropathy and pain in diabetic patients. MG increases intracellular calcium in sensory neurons and produces behavioral nociception via the cation channel transient receptor potential ankyrin 1 (TRPA1). However, rigorous characterization of an animal model of methylglyoxal-evoked pain is needed, including testing whether methylglyoxal promotes negative pain affect. Furthermore, it remains unknown whether methylglyoxal is sufficient to activate neurons in the spinal cord dorsal horn, whether this requires TRPA1, and if the calcium-sensitive adenylyl cyclase 1 isoform (AC1) contributes to MG-evoked pain. We administered intraplantar methylglyoxal and then evaluated …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations and 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 …

Repeated Plyometric Exercise Attenuates Blood Glucose In Healthy Adults, Saldiam R. Barillas, Casey M. Watkins, Megan A. Wong, Ian J. Dobbs, David C. Archer, Cameron N. Munger, Andrew J. Galpin, Jared W. Coburn, Lee E. Brown

International Journal of Exercise Science

International Journal of Exercise Science 10(7): 1076-1084, 2017. Plyometric exercise is popular in commercial exercise programs aiming to maximize energy expenditure for weight loss. However, the effect of plyometric exercise on blood glucose is unknown. The purpose of this study was to investigate the effect of relatively high intensity plyometric exercise on blood glucose. Thirteen subjects (6 females age= 21.8 ± 1.0 yrs.; height= 163.7 ± 7.8 cm; mass= 60.8 ± 6.7 kg and 7 males age= 22.0 ± 2.6 yrs.; height= 182.3 ± 3.6 cm; mass= 87.4 ± 12.5 kg) volunteered to participate. Subjects completed two random conditions on …

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 …

The Efficacy Of Tgfβ Inhibition Via Sgi-1252 In The Prevention And Reversal Of Diet-Induced Obesity And Diabetes, Blake Dallon, Benjamin Bikman

Journal of Undergraduate Research

The growing worldwide incidence of obesity and its associated pathologies, like type 2 diabetes, has received much deserved attention. However, despite this attention and substantial research efforts, little meaningful progress has been made in slowing or reversing the growing cost and trends of obesity worldwide.

As of 2008, almost 10% of medical costs in the United States were incurred due to obesity or other obesity-related diseases¹, with a substantial amount of this cost stemming from the dramatically increased risk of diabetes with excess fat mass². According to the US Centers for Disease Control and Prevention, more …

The Effect Of Acute Hyperglycemia On Muscular Strength, Power And Endurance, Franklin Lime-Ma, Joshua A. Cotter, Evan E. Schick

International Journal of Exercise Science

International Journal of Exercise Science 10(3): 390-396, 2017. The purpose of this study was to elucidate the impact of acute hyperglycemia on skeletal muscle strength, power, and endurance. Ten male collegiate athletes (age 21.5 ± 1.5 years, height 186 ± 2.03 cm, body mass 108.8 ± 7.6 kg) participated in 2 testing sessions, separated by 7 days and randomized for either high glucose (HG) or control (C) treatment conditions. HG consumed a high glucose drink (2 g glucose/kg body weight) while controls consumed an isocaloric nutrition bar (40% protein, 30% fat, and 30% carbohydrate). Blood glucose (BC) levels for HG …

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 …

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 …

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 …

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 …

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 …

Glutathione S-Transferase P In Glucose Homeostasis In Mice., Shubha Ghosh Dastidar

Electronic Theses and Dissertations

High calorie diets have fostered the current pandemic of obesity and comorbid conditions of non-alcoholic fatty liver disease (NAFLD), systemic insulin resistance (IR) and type 2 diabetes (T2D). Hepatic glutathione S-transferases (GSTs) are dysregulated in obesity, NAFLD and diabetes. The multifunctional GST pi isoform (GSTP) catalyzes acrolein metabolism and inhibits JNK (c-Jun NH₂-terminal kinase). The purpose of this study was to test specifically whether GSTP deficiency disturbs glucose homeostasis in mice. Hepatic GST proteins were downregulated by short-term high fat diet (HFD) in wild type (WT) mice concomitant with glucose intolerance, increased hepatic JNK activation and protein-acrolein …