Physiology Commons^™

The Effects Of Resistance Exercise Training On Insulin Resistance Development In Female Rodents With Type 1 Diabetes, Mitchell James Sammut

Electronic Thesis and Dissertation Repository

The etiology of insulin resistance (IR) development in type 1 diabetes mellitus (T1DM) remains unclear; however, impaired skeletal muscle metabolism may play a role. While IR development has been established in male T1DM rodents, female rodents have yet to be examined in this context. Resistance exercise training (RT) has been shown to improve IR and is associated with a lower risk of hypoglycemia onset in T1DM compared to aerobic exercise. Additionally, the molecular mechanisms mediating RT-induced improvements in insulin sensitivity remain unclear. Therefore, the purpose of this study was to investigate the effects of RT on IR development in female …

Effect Of Rearing Conditions On The Allocation Of Larval And Adult Acquired Essential And Nonessential Fatty Acids To Flight In Two Adult Lepidoptera: Danaus Plexippus And Mythimna Unipuncta, Libesha Anparasan

Electronic Thesis and Dissertation Repository

Insects which are nectivorous as adults acquire essential fatty acids, which are important for many biological processes, almost exclusively from the larval diet. Thus, adult allocation of this limited resource may result in trade-offs in migrant insects that delay reproduction. I used the true armyworm, Mythimna unipuncta, and monarch butterfly, Danaus plexippus, to test the hypothesis that environmental cues (fall migratory or summer reproductive) would influence the use of fatty acids during flight (0-6h). I used larval and adult diets manipulated isotopically (δ¹³C) and chromatographic analyses to determine fatty acid composition and source in the fat …

The Effect Of Central Chemoreceptors On The Peripheral Respiratory Chemoreflex Response To Hypoxia In Humans, Nasimi A. Guluzade

Electronic Thesis and Dissertation Repository

We measured the peripheral chemoreflex sensitivity to hypoxia (PChS) at various isocapnic carbon dioxide tensions (PCO₂) to determine the form of the relationship between PChS and central PCO₂. Twenty participants completed three repetitions of modified rebreathing tests with end-tidal PO₂ (P_ETO₂) clamped at 150, 70, 60, and 45 mmHg. PChS was computed at 1-mmHg intervals of P_ETCO₂ as follows: the differences in V̇_E between the three hypoxic profiles and the hyperoxic profile (∆V̇_E) were calculated; three ∆V̇_E values were plotted against corresponding calculated oxyhemoglobin …

The Sympathetic Neural Control Of The Circulation At Rest And During Exercise: Effects Of Age, Biological Sex, And Sex Hormones, Andrew W. D'Souza

Electronic Thesis and Dissertation Repository

The overall objective of this dissertation was to determine the impact of age, sex, and sex hormones on the discharge behaviours of muscle sympathetic action potentials (APs) as well as the corresponding changes in peripheral vasoconstriction and blood pressure at rest and during exercise. The microneurographic technique was employed to record multi-unit muscle sympathetic nerve activity (MSNA), with a continuous wavelet transform applied post-hoc to evaluate APs within the recorded neurogram. Study One examined the impact of aging on the central and peripheral arcs of the sympathetic baroreflex under resting conditions. This study revealed that middle-aged-to-older adults demonstrated heightened sympathetic …

Does Acute Maximal Exercise Or Chronic Physical Activity Affect Circulating Angiotensin (1-9) Concentrations?, Kyle R. Weiman

Electronic Thesis and Dissertation Repository

Introduction: Epidemiological evidence suggests physical inactivity can increase the likelihood of hospitalization from the SARS-COV-2 virus. Further, some data indicate a greater ratio of angiotensin 1-9 to angiotensin I helps prevent severe outcomes during infection. Moreover, related hormones can enhance potentially both physical activity and health. The purpose of this study was to determine whether plasma concentrations of angiotensin (1-9) are modified after a single exhaustive exercise bout and whether sex or chronic physical activity is associated with greater plasma concentrations.

Methods: Participants (n=14) performed a graded exercise test on a cycle ergometer. Antecubital area venipunctures were performed before, immediately …

The Effect Of Dietary Thiaminase On Cardiac Function And Morphology In Lake Trout (Salvelinus Namaycush), Peter Baker

Electronic Thesis and Dissertation Repository

Thiamine deficiency from the consumption of invasive, high-thiaminase prey fishes is considered to be a major barrier for lake trout restoration in the Great Lakes. In fishes, an understudied aspect of thiamine deficiency is its effect on cardiac function. I examined the effects of dietary thiaminase on cardiac function and morphology in lake trout, specifically as they relate to thermal tolerance. Two hatchery strains of lake trout (Seneca and Slate) were raised on a control or thiaminase diet for nine months. The thiaminase diet was associated with significant ventricle enlargement, impaired cardiac function, and reduced thermal tolerance; these effects were …

Plantar Flexor Dynamic Contractile Rates Are Not Dependent On Calcaneal Tendon Stiffness, Sohum Kulkarni

Electronic Thesis and Dissertation Repository

The ability to rapidly generate muscular torque and velocity is important in specialized activities and daily tasks of living. Tendon stiffness is one factor in the neuromuscular system that influences musculoskeletal torque transmission. Previous studies have reported weak-to-moderate correlations between tendon stiffness and rate of torque development (RTD). However, these correlations have been reported only for isometric contractions which may not be relevant to contractions involving joint rotation (i.e., dynamic). The purpose was to investigate the effect of calcaneal tendon stiffness on the dynamic rates of torque (RTD) and velocity (RVD) development in plantar flexor muscles. Young adult males (n=13) …

The Effect Of Oatp2b1-Mediated Statin Transport On Beta Cell Dysfunction, Jihoon Kwon

Electronic Thesis and Dissertation Repository

Statins are a class of cholesterol-lowering drugs which work by inhibiting the mevalonate pathway. Statin treatment has been linked to an increase in the risk of new-onset diabetes mellitus, and previous studies have suggested impairment in insulin secretion following statin treatment. Recent work from our laboratory confirmed the expression of organic anion transporting polypeptide 2B1 (OATP2B1), an important statin uptake transporter, in human pancreatic beta cells. Our study examined the role of OATP2B1 in statin-associated beta cell toxicity using INS-1 cells as a beta cell model. We showed that OATP2B1 augments cellular accumulation of rosuvastatin and atorvastatin, but not pravastatin. …

Prefrontal Coding Of Naturalistic Working Memory: Mechanisms During Normal Maintenance And Modelled Disease, Megan P. Roussy

Electronic Thesis and Dissertation Repository

Neural activity in the primate lateral prefrontal cortex (LPFC) has been causally linked to working memory (WM) ⁠— the brief maintenance and mental manipulation of information. Primates use WM to perform tasks in complex contexts; however, neural mechanisms of WM and the pathophysiology related to WM deficits have traditionally been studied using simple tasks that deviate from naturalistic conditions. This raises the question, how is WM processed in naturalistic conditions? To explore this, I trained two macaque monkeys on a spatial WM task set in a naturalistic virtual environment. During the task, a target was presented in 1 of 9 …

The Effect Of Breathing Patterns Common To Competitive Swimming On Gas Exchange And Muscle Deoxygenation During Heavy-Intensity Fartlek Exercise, Kevin J. Grossman

Electronic Thesis and Dissertation Repository

The purpose of this study was to compare the respiratory and muscle deoxygenation (HHb) responses of regulated breathing versus free-breathing, during continuous exercise (CONLD) and intermittent 5s breath holds (BH) (CONLD-BH), intermittent 5s sprint (FLK) and combined 5s BH and sprint (FLK-BH) followed by 25s of free-breathing. Oxygen uptake(V̇O₂)was unchanged between CONLD (2.12±0.35L/min) and CONLD-BH (2.15±0.42L/min; p=0.116), and FLK (2.24±0.40L/min) and FLK-BH (2.20±0.45L/min; p=0.861). Δ[Hb_tot]: CONLD (3.3±1.6µM) > CONLD-BH (-2.5±1.2µM; ∆177%; p<0.001), but unchanged between FLK (2.0±1.6µM) and FLK-BH (0.82±1.4µM; p=0.979). Δ[HHb]: CONLD (7.3±1.8µM) > CONLD-BH (7.0±2.0µM; ∆4%; p=0.011), and FLK (6.7±1.8µM) < FLK-BH (8.7±2.4µM; p<0.001). It is suggested that the unchanged V̇O₂ between CONLD and CONLD-BH was supported by increased deoxygenation, reflected by decreased ∆[Hb_tot] and blunted …

Biochemistry Of Trehalose Accumulation In The Spring Field Cricket, Gryllus Veletis, Alyssa R. Stephens

Electronic Thesis and Dissertation Repository

The freeze tolerant spring field cricket, Gryllus veletis, accumulates trehalose in the blood and tissues during cold acclimation. Trehalose is the main blood sugar in insects, thus its blood concentration is tightly regulated, and trehalose is readily metabolized. How do crickets modify their metabolism to accumulate trehalose in their hemolymph and tissues? I hypothesized that trehalose production, transport, and consumption were modified during the cold acclimation to facilitate trehalose accumulation. Trehalose and the trehalose-specific transporter, TRET-1, are distributed among all tissues, and trehalose accumulates in the hemolymph, fat body, Malpighian tubules, and gut. Trehalose production increases during cold acclimation …

The Hydrophobic Residues In Amino Terminal Domains Of Cx46 And Cx50 Are Important For Their Gap Junction Channel Ion Permeation And Gating, Roa'a Jaradat

Electronic Thesis and Dissertation Repository

Connexins are ubiquitous transmembrane proteins that assemble to form intercellular channels, called gap junctions (GJs). The amino terminal (NT) domain and residues within this domain have been shown to be important for both V_j-gating and single channel conductance (γ_j) of several GJs including Cx46 and Cx50. High-resolution structures of Cx46 and Cx50 GJs were recently resolved showing that NT domain folds into the inner pore where hydrophobic residues are packed against M1/2 domains stabilizing open-state conformation. We studied functional properties of GJs formed by several point variants at NT (Cx46 L10I, N13E, A14V, Q15N and Cx50 …

Increased Corticospinal Inhibition Following Submaximal And Maximal Muscle Activation In Humans, Alexander D. Paish

Electronic Thesis and Dissertation Repository

Following short duration, high intensity muscle activation, there is an enhancement of muscle contractile properties, termed postactivation potentiation (PAP). Corticospinal inhibition, assessed by an increased silent period (SP), was shown previously to increase following voluntary or electrically evoked PAP. Although these changes coexist, the direct effect of PAP on corticospinal inhibition has not been systematically evaluated. In 10 participants, SP duration was measured pre and post 10s maximal and submaximal, voluntary and electrically stimulated contractions. Following maximal contractions, mean twitch torque was enhanced ~180% with no enhancement at submaximal levels (~102%). The SP duration was prolonged following all conditions: ~12% …

The Impact Of Excess Nutrients, Fatty Acids Or Glucose, On Bewo Placental Trophoblast Metabolic Function, Zachary Jw Easton

Electronic Thesis and Dissertation Repository

An adverse intrauterine environment high in circulating nutrients in pregnancies complicated by maternal obesity and diabetes mellitus has been well linked with the development of metabolic health disorders in the exposed offspring. Impairments in placental development, mitochondrial respiration, and nutrient processing are thought to specifically underlie the in-utero programming of these metabolic diseases. In these “at-risk” pregnancies a maternal diet high in fat as well as poor glycemic control have been highlighted to be important regulators of placental metabolic functions (including the transport, storage, and oxidation of dietary nutrients), and consequently regulators of offspring metabolic health outcomes. However, the independent …

Collagen Iv-Β1integrin Regulation Of Exocytotic Machinery In Pancreatic Beta-Cell Insulin Secretion, Malina Barillaro

Electronic Thesis and Dissertation Repository

Diabetes is a prevalent metabolic disease characterized by impaired insulin secretion, action, or both. β1-integrin is a key receptor that regulates cell-ECM interactions and is important in maintaining beta-cell functions, including insulin secretion. However, little is reported about the relationship between β1-integrin and the exocytotic proteins involved in insulin secretion. This study examined the influence of ECM-mediated β1-integrin activation on exocytotic machinery involved in insulin secretion using rat insulinoma (INS-1) cells. Collagen IV (COL IV) promoted INS-1 cell adhesion, spreading, and insulin secretion. Additionally, these cells displayed changes in levels and localization of exocytotic proteins involved in insulin secretion. β1-integrin …

Temperature-Dependent Developmental Plasticity In The Cardiorespiratory System Of Atlantic Salmon, Carlie A. Muir

Electronic Thesis and Dissertation Repository

Anthropogenic climate change is expected to have pervasive impacts on the performance and viability of fishes, as increasing temperatures create aerobically constrained environments for many species. Given the rapid rates of projected temperature increases, it is critical to evaluate the capacity for fish to respond to a changing thermal environment through phenotypic plasticity. In this thesis, I examined the capacity for developmental plasticity in the thermal performance of juvenile Atlantic salmon (Salmo salar) reared under two thermal regimes from fertilization, and investigated potential mechanistic underpinnings within the cardiorespiratory system. Cardiac performance was examined using a noninvasive Doppler echocardiograph …

Mechanisms Of Diapause And Cold Tolerance In The Colorado Potato Beetle, Jacqueline E. Lebenzon

Electronic Thesis and Dissertation Repository

Many temperate insects enter diapause (a state of dormancy) and enhance their cold tolerance to survive the winter. During diapause, the Colorado potato beetle (CPB, Leptinotarsa decemlineata, Coleoptera: Chrysomelidae) stops developing, lowers its metabolism, and changes its physiology to avoid freezing. The extent to which diapause confers cold tolerance in CPB is currently unknown. In my thesis, I used CPB to improve our understanding of the mechanisms underlying metabolic suppression during diapause and cellular protection at sub-zero temperatures in insects. First, I used RNA-sequencing (RNA-seq) to compare gene expression in two metabolically important tissues (the fat body and flight muscle) …

Targeting Ccn Proteins In The Treatment Of Dermal Fibrosis, Alex Peidl

Electronic Thesis and Dissertation Repository

Fibrotic disorders, including the inflammatory connective tissue disease systemic sclerosis (SSc), contribute to 45% of deaths in the Western world. Currently there is no universally agreed-upon treatment for fibrosis. The CCN family of matricellular proteins are tightly spatiotemporally regulated proteins involved in development and wound healing, and are aberrantly expressed in fibrotic disease, including in SSc. CCN1 and CCN2 are overexpressed in SSc and contribute to the progression of animal models of fibrosis. CCN3 is reciprocally regulated to CCN1 and CCN2 and has been shown to suppress CCN2-mediated fibrogenic activity in kidney fibrosis. This led to the development of therapeutic …

Direct Electrical Stimulation Of Prefrontal Cortex Modulates The Transient Heart Rate Response To Exercise In Conscious Humans, Bartek Kulas

Electronic Thesis and Dissertation Repository

Prefrontal cortical regions play an essential role in generating appropriate cardiovascular adjustments, particularly in cardio-vagally mediated heart rate (HR) responses to active tasks. Functional imaging studies provide correlational evidence that this region coordinates HR responses to exercise, however, direct experimental evidence of prefrontal cortical HR regulation in humans is not available. Seven persons with epilepsy implanted with intracranial electroencephalography (iEEG) completed 2-second isometric handgrip (IHG) contractions at no-stimulation (NO-STIM) or sham-stimulation (SHAM) conditions, and during direct electrical stimulation (STIM) of the orbitofrontal and medial prefrontal cortex. HR responses to IHG during NO-STIM and SHAM increased HR by Δ4.9±2.7 bpm, compared …

Fatty Acid Regulation Of The Nrf2/Keap1 Pathway During Mouse Preimplantation Embryo Development, Grace Dionne

Electronic Thesis and Dissertation Repository

Obese women experience frequent infertility; obesity-conditioned reproductive tracts expose embryos to stressors including free fatty acids (FFA). Palmitic acid (PA) exposure significantly impairs mouse preimplantation development and increases endoplasmic reticulum stress; oleic acid (OA) rescues these effects. To further understand FFA in preimplantation development, this thesis investigates the NRF2/KEAP1 pathway, which coordinates antioxidant stress response pathways. We hypothesize that PA induces the NRF2/KEAP1 pathway, while OA alleviates it. Female mice were super-ovulated, mated, and embryos were placed in culture treatments: bovine serum albumin (control), 100 µM PA, 100 µM OA, or 100 µM PA+OA. Protein localization and mRNA abundances were …

Characterizing The Structural, Biophysical And Functional Effects Of S-Glutathionylation On Stim1 Ca2+ Sensing, Christian Michael Sirko

Electronic Thesis and Dissertation Repository

Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca²⁺) sensing protein that initiates cytoplasmic Ca²⁺ influx via store-operated calcium entry (SOCE). STIM1, in conjunction with Orai, a plasma membrane (PM) protein, function as mediators of SOCE through the formation of calcium-release activated calcium (CRAC) channels. S-Glutathionylation of STIM1 at Cys56 has been shown to evoke constitutive Ca²⁺ entry in DT40 cells, however no studies have carefully investigated the biophysical and structural effects of this covalent modification to the luminal domain, which are critical for understanding the molecular mechanism underlying the regulation of …

Investigation Of The Hsp90 Co-Chaperone, Sti1, In Cellular Resilience And Neurodegenerative Diseases, Rachel E. Lackie

Electronic Thesis and Dissertation Repository

In neurodegenerative diseases, certain proteins misfold and form toxic aggregates that cause brain matter atrophy, leading to decline in motor and/or cognitive functions. To maintain cellular proteostasis and survival, molecular chaperones regulate protein maturation and help to prevent aberrant protein aggregation. The molecular chaperone Hsp90 regulates hundreds of proteins and interestingly, several of those are misfolded in neurodegenerative diseases. Stress inducible-phosphoprotein-1 (STI1, STIP1), an Hsp90 co-chaperone, orchestrates client protein transfer between chaperones Hsp70 and Hsp90 through physical interactions with both chaperones. Notably, previous work in yeast, worms, and mouse neurons all showed that STI1 protects organisms against stressors and amyloid-like …

Cerebrovascular Compliance In Humans, Marcy Erin Moir

Electronic Thesis and Dissertation Repository

Pulsatile blood flow consists of two components: steady flow and oscillatory flow. Steady blood flow is primarily regulated by vascular resistance while vascular compliance represents a key mediator of oscillatory blood flow. However, most studies investigating the regulation of cerebral blood flow in humans have focused on vascular resistance. Recently, emerging evidence has implicated vascular compliance as an important contributor to the regulation of cerebral perfusion. Therefore, the research contained herein aimed to i) quantify cerebrovascular compliance responses to blood pressure alterations and ii) explore mechanisms regulating cerebrovascular compliance in humans. The studies employed a Windkessel modelling approach to calculate …

Examining The Feasibility Of Delivering A Multi-Component Virtual Lifestyle Medicine Program For Adults With Type 2 Diabetes, Madison S. Hiemstra

Electronic Thesis and Dissertation Repository

BACKGROUND: The virtual delivery of lifestyle medicine programs (e.g., via web-conferencing platforms) can increase program accessibility for adults living with type 2 diabetes (T2D). PURPOSE: To assess the feasibility of virtually delivering a multi-component group-based lifestyle medicine program that uses wearable technologies and exercise prescriptions in an adult population with T2D. METHODS: This was a six-week, single-cohort feasibility study. The virtual lifestyle medicine program included live-video delivery of group education classes, one-on-one exercise counselling phone calls, flash glucose monitors, wearable activity monitors, and exercise prescriptions. Several feasibility outcomes were assessed including recruitment and retention rates, acceptability (e.g., exit survey), and …

21°C Is The Emerging Ideal Temperature For Kidney Preservation In The Presence Of Hydrogen Sulfide, Smriti Juriasingani

Electronic Thesis and Dissertation Repository

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, the shortage of transplantable kidneys has led to ever-increasing waiting lists. As a result, kidneys obtained via donation after cardiac death (DCD) are being used more frequently for transplantation. However, they exhibit poorer outcomes due to ischemia-reperfusion injury (IRI) and cold preservation methods, such as static cold storage (SCS). Supplementing cold preservation solutions with hydrogen sulfide donors, such as AP39, has been shown to improve renal IRI and graft outcomes, but the injury associated with cold preservation remains. This thesis evaluates the effect of subnormothermic kidney …

Spinal Excitability Changes Following Sensory Electrical Stimulation Of The Forearm, Devin K. Box

Electronic Thesis and Dissertation Repository

Sensory electrical stimulation can be used to suppress tremor in Parkinson’s disease. This study investigated the central mechanism underlying this suppression in healthy participants. Reciprocal inhibition (RI) of the wrist flexors before and after a session of sensory electrical stimulation (SES) applied to the antagonistic extensor muscles was assessed using electromyography. It was hypothesized that a 15-minute session of SES, rated by participants as a 3 on a 0-10 pain scale, would produce an increase in RI. Seven of the 18 participants experienced an increase in RI at 0-5 minutes post stimulation, which returned to baseline at 10-15 minutes. The …

Characterizing The Effects Of Pyrroloquinoline Quinone (Pqq) Supplementation On Skeletal Muscle Mitochondrial Function And Myogenesis During Oxidative Stress And Iugr., Allyson J. Wood

Electronic Thesis and Dissertation Repository

Intrauterine growth restriction (IUGR) affects 10-15% of births and is associated with placental insufficiency (PI), resulting in fetal oxidative stress (OS). This OS is a factor in the predisposition to postnatal noncommunicable disease (NCD) of which muscle mitochondrial dysfunctional is a key aspect. Pyrroloquinoline quinone (PQQ), an antioxidant-like compound, is capable of OS reduction and promotes mitochondrial function, though limited research has focused on its effects in in utero skeletal muscle. This study sought to investigate the impact of in vitro H₂O₂, a model of OS, and an in vivo model of OS associated IUGR, with …

Inwardly Rectifying Potassium Channels: Regulators Of Myogenic Tone In Cerebrovascular Smooth Muscle, Jacob Fletcher

Electronic Thesis and Dissertation Repository

In cerebral arteries, inwardly rectifying potassium channels (K_IR) contribute to smooth muscle hyperpolarization to control arterial diameter and tone. Emerging evidence highlighted their regulation by pressure, though the underlying mechanism remains unclear. This thesis explored this concept through examination of K_IR channels in mouse and rat cerebral vascular smooth muscle (VSM). Experiments progressed from isolated cells to whole animals, employing electrophysiology, immunocytochemistry, proximity ligation assay, and arterial spin-labelling MRI techniques. Initial experiments indicated that K_IR activity persists beyond K_IR2.1 knockout in smooth muscle, clarifying their molecular composition. Our subsequent study identified key structural components …

Sexual Dimorphism In Response To Repetitive Bouts Of Acute Exercise In Rodents With Type 1 Diabetes Mellitus, Jordan C. Larocque

Electronic Thesis and Dissertation Repository

The purpose of this study was to examine sex-specific differences in the blood glucose (BG) response to recurrent aerobic exercise in type 1 diabetes. Specifically, we examined the role of peak estrogen (E2) concentrations during proestrus on BG response to prolonged aerobic exercise. To do so, nineteen Sprague-Dawley rats were assigned to four exercised groups: control female (CXF; n = 5), control male (CXM; n = 5), diabetic female (DXF, n = 5) and diabetic male (DXM, n = 4). Diabetes was induced in DX groups via subcutaneous injection of low dose streptozotocin. After four days of exercise, liver glycogen …

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson

Electronic Thesis and Dissertation Repository

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …