Effect of Chronic, Low-Dose TCDD Exposure on Glucose Homeostasis and Beta Cell Function in Wild Type and Cyp1a1/1a2 Systemic Knock-Out Adult Mice

Exposure to persistent organic pollutants (POPs) is associated with increased diabetic pathology. The goal of my thesis was to understand how chronic, low dose exposure to a model POP, 2,3,7,8-tetracholorodibenzo-p-dioxin, promotes diabetic pathology in C57BL/6 mice and the role of Cyp1a1/1a2 enzymes during exposure. My first aim was to determine the effect of chronic, low dose TCDD exposure in wild type and systemicCyp1a1/1a2knock-out mice on glucose homeostasis and β-cell function. My second aim was to determine the effects of direct, low dose TCDD exposure in isolated pancreatic islets with and withoutCyp1a1/1a2gene deletion. My third aim was to determine the effect of concurrent high-fat diet (HFD) and TCDD exposure in wild type mice on glucose homeostasis and β-cell function. I found sex differences in the role of Cyp1a1/1a2 in insulin secretion during TCDD exposurein vitroand during concurrent TCDD exposure and HFD-feedingin vivo.