Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item INVESTIGATION OF DISRUPTED INSULIN SIGNALING IN A SWINE MODEL(2024) Markley, Grace Irene; Stahl, Chad H; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Insulin is an anabolic hormone involved in glucose uptake and synthesis of fats, proteins, and glycogen. Domesticated livestock species such as swine require efficient insulin signaling to meet production demands across the world. Insulin signaling is tightly regulated and acts on metabolic tissues such as the liver, skeletal muscle, and adipose tissue. The most well characterized disruption of insulin signaling is insulin resistance that is often caused by obesity induced inflammation. However, insulin signaling can be disrupted via atypical mechanisms such as immune response to a pathogen and adaptor proteins. We aimed to evaluate the impact of pathogen exposure and intrinsic adaptor proteins on insulin signaling in pigs. The first study focuses on the impact of growth factor receptor bound protein 10 (GRB10) as an inhibitor of insulin signaling. In commercial swine, the presence of GRB10 has been linked to growth, reproduction, feed efficiency and lean muscle growth. While insulin induces glucose uptake in typical tissues, such as the liver and skeletal muscle, insulin also acts on other cell types including mesenchymal stem cells (MSC). MSC are adult multipotent stem cells that can self-renew and differentiate into multiple cell types including adipocytes. The process of adipogenesis requires insulin signaling to synthesize new triglycerides and store them in lipid droplets. While GRB10 has been established as a regulator of insulin signaling, the role of GRB10 in swine MSC has yet to be firmly established. We generated GRB10 knockdown (GRB10-KD) MSC to evaluate the impact of GRB10 on insulin signaling and glucose uptake. We observed reduced glucose utilization under basal conditions and reduced insulin signaling when incubated with insulin over 48 hours. We also noticed a two-fold reduction in proliferation rate among GRB10-KD MSC. When differentiated into adipocytes, we observed an increase in transcript abundance with genes associated with insulin signaling and adipogenesis. GRB10 has the potential to regulate insulin signaling in swine MSC and contribute to overall growth and development. The second chapter focuses on the impact of lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, which can induce a severe, systemic immune response. In pigs, chronic LPS exposure has induced insulin resistance. However, the effects of acute exposure to LPS on insulin signaling and resistance have not been elucidated. We found that acute exposure to LPS in crossbred post-weaning pigs induced changes in insulin signaling and glucose metabolism. There was an LPS induced decrease in insulin two hours after injection which was paired with hyperglycemia. At 24 hours post LPS there was a marked insulin resistance indicated by hyperinsulinemia and hyperglycemia. We also noted that there were liver specific decreases in genes associated with glucose metabolism, insulin signaling and fatty acid metabolism. As well as reduction in protein abundance such as protein kinase B (AKT) and phosphoinositide-3 kinase (PI3K) in the liver after LPS administration. During an acute exposure to endotoxin, insulin signaling, and glucose metabolism is reduced in the liver. These results highlight that insulin signaling is a complex and dynamic process that can be controlled through a variety of mechanisms and swine can serve to model these disruptions.Item THE EFFECTS OF LOW-VOLUME/MODERATE-INTENSITY AEROBIC TRAINING ON METABOLIC SYNDROME COMPONENTS IN MORBIDLY OBESE MINORITY ADOLESCENTS(2010) Many, Gina Marie; Hagberg, James M.; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Despite the increased prevalence of obesity and associated diseases among pediatric minorities, the intensity-specific effects of aerobic training have not been examined extensively in adolescent minorities. Fifteen morbidly obese, sedentary and insulin-resistant Black and Latino adolescents completed two-months of low-volume/moderate-intensity aerobic exercise training to examine the effects of training on three phenotypes dysregulated in obese and physically inactive states: insulin sensitivity (SI); fibrinolytic potential, as indicated by plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) antigen levels; and chronic low-grade systemic inflammation, as indicated by C-reactive protein (CRP). In response to training, SI increased ~37% (1.00 ± 0.15 to 1.37 ± 0.26 mU.L^-1min^-1, p<0.05) and t-PA antigen levels increased ~15% (6.34 ± 0.51 to 7.32 ± 0.85 ng/mL, p<0.05). No significant changes in CRP or PAI-1 antigen were observed. Our findings demonstrate that aerobic training improves insulin sensitivity and fibrinolytic potential in morbidly obese minority adolescents.