Dissertation/Thesis Abstract

Effects of a DGAT1 Inhibitor and a Peroxynitrite Decomposition Catalyst on Human β-cell Function and Survival under Chronic Nutrient Overload
by Johns, Michael Eugene, II, M.S., Southern Illinois University at Edwardsville, 2014, 60; 1561302
Abstract (Summary)

The rate at which people are diagnosed with type 2 diabetes mellitus (T2DM) increases every year adding to the millions worldwide already affected. This is primarily due to the growing trend in obesity. Over time, excess dietary nutrients cause the dysfunction and death of β-cells, the only endogenous source of insulin. Continued research on β-cell metabolic alterations in response to excess nutrients may provide valuable insight for developing new anti-diabetic agents to help combat the growing T2DM epidemic. Our recent studies involved two such agents, SR-135 and BN-99. SR-135, a peroxynitrite decomposition catalyst, effectively improved the glucose tolerance and insulin sensitivity of diet-induced diabetic mice. BN-99, a DGAT1 inhibitor, preserved the function of human β-cells in vitro despite being cultured with excess nutrients. The following research was driven by the results of our two previous studies to help better understand the effects of these agents. Human pancreatic islets were cultured in vitro under two different levels of excess nutrients and the effects of SR-135 and BN-99 on four different measures of cellular health were recorded. Results indicated that both agents reduced nitrotyrosine formation and prevented caspase-dependent apoptosis. In addition, BN-99 was found to increase mitochondrial density in β-cells, a consequence that warrants further study (Wild et al., 2004).

Indexing (document details)
Advisor: Kwon, Guim
Commitee: Jennings, David, Liebl, Faith, Neumann, William
School: Southern Illinois University at Edwardsville
Department: Biological Sciences
School Location: United States -- Illinois
Source: MAI 53/04M(E), Masters Abstracts International
Subjects: Molecular biology, Pharmacy sciences
Keywords: Beta cells, Diabetes, Insulin, Nitrotyrosine, Peroxynitrite
Publication Number: 1561302
ISBN: 9781321063165