This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Cellulose, a major constituent of biomass, is a promising source of sustainable energy. A key step in the conversion of cellulose to a platform chemical is glucose isomerization to fructose. Sn-Beta zeolite catalyzes this reaction with high yield. The effect of methanol as a reaction medium on glucose transformations catalyzed by Sn-Beta has not been quantified. Here, density functional calculations are employed to elaborate on the effect of methanol medium, specifically to determine how reaction pathways and energy barriers are affected by methoxylation of Sn or Si groups at the active sites in Sn-Beta. Calculations suggest that the presence of the neighboring silanol group is necessary for glucose isomerization. If the silanol group is altered by methoxylation glucose epimerization is promoted and will likely occur. These results provide additional understanding of the active site of Sn-Beta for glucose transformations and are insightful for novel catalyst design and development.

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The prevalence of obesity is increasing globally. Obesity is characterized by increased fat mass and is a risk factor for type 2 diabetes (T2D). Obesity is associated with hyperglycaemia, hyperinsulinemia, insulin resistance and chronic inflammation. Currently, the most effective and durable treatment for obesity and its comorbidities is bariatric surgery. Bariatric surgery changes food intake, energy balance and the composition of gut microbiota. Bariatric surgery can lower blood glucose and put T2D into remission. It was unknown if bariatric surgery-induced changes in the gut microbiota was an independent yet sufficient factor to lower blood glucose. Fecal microbiota transplantation (FMT) was performed on conventional (specific-pathogen-free, SPF) and germ-free (GF) mice using fecal material obtained from patients before surgery and 12 months after bariatric surgery. We tested FMT into mice from the same patients before and after vertical sleeve gastrectomy (VSL) and biliopancreatic diversion with duodenal switch (BPD/DS). FMT did not alter body weight, fat mass, glucose tolerance or glucose transporter mRNA expression in all intestine segments in SPF mice. FMT lowered blood glucose during an oral glucose load in GF mice receiving bacteria after VSL and BPD/DS bariatric surgery. Post-BPD/DS surgery FMT decreased Glut1 transcript level in the ileum and increased Glut1 transcript level in the TA muscle of GF mice, but did not change GLUT1 protein levels. Post-BPD/DS surgery FMT also decreased goblet cell count, villus height and crypt depth in the ileum of GF mice. We conclude that changes in the gut microbiota caused by bariatric surgery is a standalone factor that can lower blood glucose and alter gut morphology. / Thesis / Master of Science (MSc) / Type 2 diabetes is a chronic disease that involves high blood sugar (i.e. glucose), which can damage many parts of the body leading to serious complications. Diabetes is a growing global problem and is the seventh leading cause of death. Obesity is one of the largest factors leading to type 2 diabetes. Bariatric surgery reduces obesity and is to date the most effective method to lower blood glucose and reverse type 2 diabetes. Bariatric surgery alters gut anatomy and the types of bacteria that inhabit the gut. Gut bacteria can change obesity and blood glucose levels, but it was not known if the bacterial community present after bariatric surgery was a factor that is sufficient to lower blood glucose. We found that transferring gut bacteria from humans after bariatric surgery into mice lowers the blood glucose and alters the gut barrier structure where food is absorbed. It is not yet clear how this happens, but these findings show that a change in gut microbes is a standalone factor that can alter host blood glucose. Finding the glucose lowering factor in bacteria may be a new treatment to combat type 2 diabetes.

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Commercial broiler chickens are withdrawn from feed prior to harvesting, transport and processing. This feed withdrawal period does not reduce carcass yield but is significant in reducing the potential for carcass contamination from undigested feed or fecal material that may remain in the digestive tract if feed is not withdrawn. However, withdrawing feed can result in an increase in bacterial contamination due to the decrease in physiological pH during fasting. Recently, consumers are more interested in how food animals are raised, prepared for, and processed. In response to these concerns, the feasibility of developing a “feed withdrawal” feed that could be provided to commercial broilers during the traditional feed withdrawal period was evaluated. The physiological effect of fasting during the feed withdrawal period is also not well understood. The focus of this study was to determine if feedstuffs that are readily accessible to commercial feed mills was evaluated to determine if body weight loss could be reduced and commercial broilers could be processed acceptably when allowed access to this feed during the traditional feed withdrawal period. In addition, the physiological response of commercial broilers at different ages to fasting was determined. The emphasis of this study was to determine the effect of fasting periods of commercial broilers on the hormones insulin and glucagon, circulating levels of glucose and body temperature compared to fulled birds. The results of this research suggests that a “feed withdrawal feed” that is available to commercial feed mills is feasible to allow commercial broilers access to feed during the traditional feed withdrawal period and still be processed with no contamination concerns. In addition, the impact of fasting on the hormones glucagon and insulin, circulating levels of glucose and body temperature were shown to be significantly changed during a fasting period.

<p> This study was designed to investigate possible changes in insulin sensitivity (IS) with cessation of training. Six endurance trained athletes were studied at 12, 60 h and 7 days following cessation of training. In-vivo IS was established by a glucose clamp technique (Greenfield et al. Diabetes 30, 1981) and expressed as the metabolic clearance rate of glucose (MCR) in ml. plasma cleared kg-1. min-1. At 12 h after the last training session the mean MCR was 15.6+1.8 compared with 7.8+1.2(p<0.01) in age and weight matched sedentary controls. The MCR decreased to 10.1+1.0 after 60 h and decreased significantly to 8.5+0.5(p<0.05) after 7 days of detraining. In-vitro IS was measured by determining the insulin binding of fractionated young erythrocytes by the method of Polychronakos et al. (Clin. Inves. Med.4,14B,1981). Insulin binding was 10.4+0.9% at 12 h and decreased significantly to 8.1+0.7%/4xl0^9 cells after 60 h of detraining (p<0.001). In conclusion: 1) detraining of endurance athletes resulted in a rapid decrease in IS. After 7 days, glucose MCR reached values indistinguishable from sedentary controls. 2) changes in IS observed may be partially mediated by alterations in insulin binding to receptors. 3) since the high IS observed with endurance athletes on the initial test disappeared shortly after cessation of training, it is probably an acute effect of the last exercise bout rather than a chronic effect of training.</p> / Thesis / Master of Science (MSc)

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

The cytokine, interleukin-7 (IL-7), has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic activity in support of its vital function in lymphocytes. We observed that IL-7 deprivation caused a rapid decline in ATP levels that were attributable to loss of intracellular glucose retention. To identify the transducer of the IL-7 metabolic signal, we examined the expression of three important regulators of glucose metabolism, the glucose transporter, GLUT-1, and two glycolytic enzymes, Hexokinase II (HXKII) and phosphofructokinase-1 (PFK1), using an IL-7-dependent T-cell line and primary lymphocytes. We found that in lymphocytes deprived of IL-7 loss of glucose uptake correlated with decreased expression of HXKII. Re-addition of IL-7 to cytokine deprived lymphocytes restored the transcription of the HXKII gene within 2 hours, but not that of GLUT-1 or PFK1. IL-7-mediated increases in HXKII, but not GLUT-1 or PFK-1, were also observed at the protein level. Inhibition of HXKII with 3-Bromopyruvate or specific siRNA decreased glucose utilization, as well as ATP levels, in the presence of IL-7, while over-expression of HXKII, but not GLUT-1, restored glucose retention and increased ATP levels in the absence of IL-7. This IL-7 mediated HXKII gene expression was abrogated with inhibition of JNK pathway. IL-7 also increased activation of AP-1 complex and DNA binding of JunD, a transcriptional complex thought to be negative regulator of proliferation. We found that over expression of HXKII caused cell cycle arrest and cell death, indicating that a potent IL-7 signal could produce negative growth signals. We conclude that IL-7 controls glucose utilization by regulating the gene expression of HXKII through activation of JNK-JunD pathway, suggesting a mechanism by which IL-7 supports bioenergetics that control cell fate decisions in lymphocytes.