Investigating a Link a between Type-1 Diabetes and Environmental Factors

Location

Room 1909

Session Format

Paper Presentation

Research Area Topic:

Natural & Physical Sciences - Biology

Abstract

Background: In the 2008-2009 report by the Center for Disease Control, an estimated 18,436 people younger than 20 years in the U.S. were newly diagnosed with type-1 diabetes (T1D) annually. The increase in the numbers of T1D incidences are thought to be related to environmental reasons such as the arylamine 2-aminoanthracene (2AA). T1D is an unpreventable, inflammatory disease of the pancreatic islet in which insulin-producing beta cells are destroyed by auto-reactive T-cells and monocytic cells. If the pancreas is not able to produce or secrete insulin, the body will not be able to metabolize glucose. It is believed that T1D is triggered by beta cell death within the pancreas. An exogenous factor such as exposure to polycyclic aromatic hydrocarbons (PAHs) can precede these inflammatory events within the organism in a T1D dependent manner. 2AA belongs to a class of PAHs and it is a carcinogen employed in the manufacture of dyes, drugs, inks, and agricultural chemicals. Previous studies have shown that exposure to this compound can lead to the dysregulation and alteration of pancreatic genes that are responsible for lipid and protein metabolism which can lead to insulin resistance and tissue autolysis. We have also found the expression of genes that play essential roles in the inflammation of the pancreas.

Objective and Hypothesis: It is prudent that we continue to examine all possible causes of T1D and the genetic basis of this disease. The purpose of this study is to find the correlation between 2-aminoanthracene (2AA) and type 1-diabetes (T1D). We hypothesize that dams that ingest 2AA during pregnancy will show systemic effects in the offspring that is inflammatory response dependent. Dams that are exposed to a higher concentration of 2AA will exhibit a higher number of alterated genes.

Methods: In this proposed study, three groups of Sprague Dawley dams will be exposed to different concentrations of 2AA through their diet. The groups will be fed 0 mg/kg- (C- Control), 50mg/kg- (LD- Low Dose) and 100 mg/kg-2AA diet (HD- High Dose) from gestation through postnatal period. Certain genes that lead to the production of cytokines and adipokines that play a significant role in inflammatory response will be analyzed in the pancreas of the pups. The genes include TNF-ë±, IL-6, CD14, CD68, LEPTIN, and GAPDH as a control gene. Furthermore, there will be an assessment of insulin, C-peptide, proinsulin, and C-reactive protein (CRP) amounts in the blood of the offspring. The anatomy of the pancreas will be evaluated to determine the size and mass of the beta cells within the pancreas. Insulin, C-peptide, proinsulin and CRP are markers of insulin activity in the pancreas.

Outcome: When this project is completed, we will be able to link environmental exposure to T1D. Through the evaluation of certain genes and natural processes within the body and the pancreas, the effect of 2-aminoanthracene on the pancreas and possible induction of T1D will be able to be determined. This information may help us prevent this induction through testing the down-regulation of specific genes and facilitating the proper secretion of lysed beta cells to prevent an autoimmune response.

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Presentation (Open Access)

Start Date

4-16-2016 9:30 AM

End Date

4-16-2016 10:30 AM

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Apr 16th, 9:30 AM Apr 16th, 10:30 AM

Investigating a Link a between Type-1 Diabetes and Environmental Factors

Room 1909

Background: In the 2008-2009 report by the Center for Disease Control, an estimated 18,436 people younger than 20 years in the U.S. were newly diagnosed with type-1 diabetes (T1D) annually. The increase in the numbers of T1D incidences are thought to be related to environmental reasons such as the arylamine 2-aminoanthracene (2AA). T1D is an unpreventable, inflammatory disease of the pancreatic islet in which insulin-producing beta cells are destroyed by auto-reactive T-cells and monocytic cells. If the pancreas is not able to produce or secrete insulin, the body will not be able to metabolize glucose. It is believed that T1D is triggered by beta cell death within the pancreas. An exogenous factor such as exposure to polycyclic aromatic hydrocarbons (PAHs) can precede these inflammatory events within the organism in a T1D dependent manner. 2AA belongs to a class of PAHs and it is a carcinogen employed in the manufacture of dyes, drugs, inks, and agricultural chemicals. Previous studies have shown that exposure to this compound can lead to the dysregulation and alteration of pancreatic genes that are responsible for lipid and protein metabolism which can lead to insulin resistance and tissue autolysis. We have also found the expression of genes that play essential roles in the inflammation of the pancreas.

Objective and Hypothesis: It is prudent that we continue to examine all possible causes of T1D and the genetic basis of this disease. The purpose of this study is to find the correlation between 2-aminoanthracene (2AA) and type 1-diabetes (T1D). We hypothesize that dams that ingest 2AA during pregnancy will show systemic effects in the offspring that is inflammatory response dependent. Dams that are exposed to a higher concentration of 2AA will exhibit a higher number of alterated genes.

Methods: In this proposed study, three groups of Sprague Dawley dams will be exposed to different concentrations of 2AA through their diet. The groups will be fed 0 mg/kg- (C- Control), 50mg/kg- (LD- Low Dose) and 100 mg/kg-2AA diet (HD- High Dose) from gestation through postnatal period. Certain genes that lead to the production of cytokines and adipokines that play a significant role in inflammatory response will be analyzed in the pancreas of the pups. The genes include TNF-ë±, IL-6, CD14, CD68, LEPTIN, and GAPDH as a control gene. Furthermore, there will be an assessment of insulin, C-peptide, proinsulin, and C-reactive protein (CRP) amounts in the blood of the offspring. The anatomy of the pancreas will be evaluated to determine the size and mass of the beta cells within the pancreas. Insulin, C-peptide, proinsulin and CRP are markers of insulin activity in the pancreas.

Outcome: When this project is completed, we will be able to link environmental exposure to T1D. Through the evaluation of certain genes and natural processes within the body and the pancreas, the effect of 2-aminoanthracene on the pancreas and possible induction of T1D will be able to be determined. This information may help us prevent this induction through testing the down-regulation of specific genes and facilitating the proper secretion of lysed beta cells to prevent an autoimmune response.