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Washington University in St. Louis

Diabetes

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Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda Aug 2021

Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda

Arts & Sciences Electronic Theses and Dissertations

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …

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Investigating The Differentiation And Functional Maturation Of Stem Cell-Derived Β Cells, Leonardo Velazco-Cruz Aug 2021

Investigating The Differentiation And Functional Maturation Of Stem Cell-Derived Β Cells, Leonardo Velazco-Cruz

Arts & Sciences Electronic Theses and Dissertations

Diabetes mellitus is a chronic and global disease rapidly growing in prevalence. Diabetes can be characterized by the dysfunction or death of the glucose sensing insulin secreting  cell.  cells are located within the islet of Langerhans (islet), a tissue within the pancreas. Human islets are critical for the study and treatment of diabetes. However, they can only be obtained from cadaveric organ donors. These cadaveric islets do not proliferate and can only be maintained in vitro for short periods of time, making their availability rare and fleeting. Stem cell-derived -like cells can be generated in indefinite amounts and …

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Midfoot And Ankle Movement Dysfunction In People With Diabetes Mellitus And Peripheral Neuropathy, Hyo Jung Jeong Jan 2021

Midfoot And Ankle Movement Dysfunction In People With Diabetes Mellitus And Peripheral Neuropathy, Hyo Jung Jeong

Arts & Sciences Electronic Theses and Dissertations

People with diabetes mellitus and peripheral neuropathy (DMPN) have midfoot and ankle musculoskeletal problems, including limited joint mobility and weakness and atrophy of foot intrinsic and calf muscles. Impaired foot structures and function could lead to midfoot and ankle movement dysfunction, measured by a heel rise task. A repeated movement dysfunction during weightbearing tasks (e.g., heel rise, walking) could cause excessive stress on the plantar tissue, which is a leading cause of plantar ulceration in people with DMPN. Understanding heel rise performance and the underlying mechanisms could help prevent the sequence of events associated with plantar ulcer development in people …

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Autologous Stem Cell-Derived Β Cells For Diabetes Cell Replacement Therapy, Kristina G. Maxwell Jan 2021

Autologous Stem Cell-Derived Β Cells For Diabetes Cell Replacement Therapy, Kristina G. Maxwell

McKelvey School of Engineering Theses & Dissertations

Autologous stem cell therapy is a promising treatment for patients with diabetes worldwide. Previous stem cell-derived β (SC-β) cell protocols were unable to efficiently differentiate multiple patient induced pluripotent stem cells (iPSCs) into stem cell-derived islets (SC-islets), containing insulin-secreting SC-β cells. Recent updates targeting the actin cytoskeleton have enabled the differentiation of 14 diabetic and nondiabetic stem cell lines into SC-islets. We used genetic engineering, specifically CRISPR/Cas9, to correct the diabetes-causing mutation in stem cells from patients with Wolfram Syndrome. The genetically engineered SC-β cells functioned and had a composition similar to nondiabetic SC-β cells, unlike the unedited SC-β cells …

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Electrophysiology Of The Inner Retina In Health And Disease: Eaat5 In The Rod Bipolar Cell And Oscillatory Potentials In Diabetes, Gregory William Bligard May 2020

Electrophysiology Of The Inner Retina In Health And Disease: Eaat5 In The Rod Bipolar Cell And Oscillatory Potentials In Diabetes, Gregory William Bligard

Arts & Sciences Electronic Theses and Dissertations

The inner retina is a highly tractable location for the study of neural networks in the central nervous system and improving our understanding of the inner retina is important for the treatment of a number of ophthalmic diseases. This dissertation aims to improve understanding of the inner retina in two parts: first, a basic neuroscientific project concerning normal neuronal processing in the inner retina at a cellular level, and second, a translational ophthalmologic project regarding the development in the inner retina of a common disease. In mammals, modulation of the amplitude of dim visual signals primarily occurs at axon terminals …

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Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel Aug 2018

Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel

Arts & Sciences Electronic Theses and Dissertations

1-in-3 persons with type 2 diabetes (T2DM) develop chronic kidney disease (CKD), which is characterized by progressive renal dysfunction leading to end-stage renal disease. In response to elevated blood glucose and systemic inflammation of diabetes, a process of active thickening of the renal glomerular basement membrane ensues with concomitant damage to the structural supports (podocytes) of the kidneyճ filtration barrier. This results in impaired renal filtration. The metabolic sequelea of T2DM and CKD also, synergistically, alter skeletal muscleճ degradative pathways, satellite cell function (muscle reparative cells), and mitochondrial health (muscle energetic machinery) -- resulting in muscle breakdown, poor muscle quality, …

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Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris Aug 2017

Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris

Arts & Sciences Electronic Theses and Dissertations

Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …

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Glucosensing, Hypoglycemia, And The Brain, Candace Reno Feb 2013

Glucosensing, Hypoglycemia, And The Brain, Candace Reno

All Theses and Dissertations (ETDs)

Glucose homeostasis can be peripherally and centrally mediated. Within the periphery, GLUT4 in muscle and adipose tissue is required for normal glucose homeostasis and disruption of GLUT4 translocation in these tissues leads to glucose intolerance and insulin resistance, hallmarks of Type 2 diabetes. Within the brain, specialized glucose sensing neurons regulate whole body glucose homeostasis. Unlike GLUT4's role in the periphery, brain GLUT4 regulation of glucose tolerance is not well defined. Understanding how brain glucose sensing, mediated by GLUT4, regulates glucose tolerance and insulin sensitivity will aid in the development of treatment strategies to protect against the pathogenesis of diabetes. …

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