Theses and Dissertations

Issuing Body

Mississippi State University

Advisor

Chambers, Janice E.

Committee Member

Howell, George Eli, III

Committee Member

Crow, John Allen

Committee Member

Ross, Matthew K.

Committee Member

Wills, Robert W.

Date of Degree

5-7-2016

Document Type

Dissertation - Open Access

Major

Veterinary Medicine

Degree Name

Doctor of Philosophy

College

College of Veterinary Medicine

Department

Environmental Toxicology Program

Abstract

Type 2 diabetes mellitus (T2D) is a metabolic disease characterized by hyperglycemia, insulin resistance, dyslipidemia, and beta cell dysfunction. T2D prevalence has been increasing with not all clear causes identified, while the use of synthetic chemicals has risen. Because genetics can only explain a small percentage of disease development, more attention is being given to associations of environmental chemical exposure and disease. Epidemiological evidence suggests environmental exposure to organochlorine compounds (OC) including dichlorodiphenyltrichloroethane (DDT) and its bioaccumulative metabolite dichlorodiphenyldichloroethylene (DDE) is associated with T2D prevalence and is hypothesized to play a role in contributing to T2D. The purpose of this research was to perform anin vitro study of DDE exposure and its effect on liver hepatocyte and pancreatic beta cell functions that regulate biochemical markers implicated in T2D, and determine an association of DDE exposure with T2D from a population exhibiting a high prevalence of T2D living in an area once highly exposed to OC. Human blood samples from diabetics and non-diabetics were analyzed for any significant association of DDE levels with biochemical markers of T2D and T2D presence. The in vitro effect of DDE exposure on the regulation of hepatocyte lipid metabolism and secretion with respect to triglyceride (TG), apolipoprotein B (ApoB), sortilin-1 (Sort-1), and microsomal triglyceride transfer protein (MTP) levels implicated in dyslipidemia was investigated. Finally, the in vitro effect of DDE exposure on the regulation of beta cell insulin secretion with respect to insulin, oxidative stress (ROS), prohormone convertase (PC), and pancreatic-duodenal homeobox-1(PDX-1) levels implicated in beta cell dysfunction was investigated. Based on our results, DDE levels were not associated with an increased risk of T2D prevalence from this study population, although DDE levels were correlated with some biochemical markers of T2D. ApoB secretion, Sort-1 and MTP levels were increased after DDE exposure, while TG accumulation was decreased in hepatocytes. Insulin secretion and PC levels were increased after DDE exposure, while ROS and PDX-1 levels were increased but not significantly. Although no causative association of DDE exposure with T2D prevalence was found, a potential mechanism of DDE’s effect on regulating biochemical markers of T2D was identified.

URI

https://hdl.handle.net/11668/17545

Comments

organochlorines||diabetes||liver

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