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A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Jingshu Chen1, Lei Zhong2, Jing Wu2
1Texas A&M University.
Abstract:
Exposure to certain environmental chemicals in human and animals has been found to cause cellular damage of the pancreatic β cells which will lead to the development of type 2 diabetes mellitus (T2DM). Although the mechanisms for the chemical-induced β cell damage were unclear and likely to be complex, one recurring finding is that these chemicals induce oxidative stress leading to the generation of excessive reactive oxygen species (ROS) which induce damage to the β cell. To identify potential diabetogenic environmental chemicals, we isolated pancreatic islet cells from C57BL/6 mice and cultured islet cells in 96-well cell culture plates; then, the islet cells were dosed with chemicals and the ROS generation was detected by 2',7'-dichlorofluorescein (DCFH-DA) fluorescent dye. Using this method, we found that bisphenol A (BPA), Benzo[a]pyrene (BaP), and polychlorinated biphenyls (PCBs), could induce high levels of ROS, suggesting that they may potentially induce damage in islet cells. This method should be useful for screening diabetogenic xenobiotics. In addition, the cultured islet cells may also be adapted for in vitro analysis of chemical-induced toxicity in pancreatic cells.
Insights
Certain environmental chemicals can damage pancreatic beta cells, increasing type 2 diabetes risk. Researchers developed a method using mouse islet cells to screen for chemicals like BPA, BaP, and PCBs that generate harmful reactive oxygen species (ROS).
Area of Science:
- Environmental Health
- Endocrinology
- Toxicology
Background:
- Environmental chemical exposure is linked to pancreatic beta cell damage and type 2 diabetes mellitus (T2DM).
- Chemical-induced beta cell damage mechanisms are complex, but often involve oxidative stress and reactive oxygen species (ROS) generation.
- Identifying diabetogenic environmental chemicals is crucial for public health.
Purpose of the Study:
- To develop and validate an in vitro method for screening environmental chemicals that induce pancreatic beta cell damage.
- To identify specific environmental chemicals that cause oxidative stress in pancreatic islet cells.
Main Methods:
- Mouse pancreatic islet cells were isolated and cultured in 96-well plates.
- Cells were exposed to various chemicals, and reactive oxygen species (ROS) generation was measured using the DCFH-DA fluorescent dye.
- High-throughput screening of potential diabetogenic xenobiotics was performed.
Main Results:
- Bisphenol A (BPA), Benzo[a]pyrene (BaP), and polychlorinated biphenyls (PCBs) were identified as chemicals that induce high levels of ROS in pancreatic islet cells.
- These findings suggest that BPA, BaP, and PCBs may be diabetogenic.
- The developed method effectively detects chemical-induced ROS generation in cultured islet cells.
Conclusions:
- The established in vitro method is effective for screening diabetogenic xenobiotics by detecting ROS production.
- Environmental chemicals such as BPA, BaP, and PCBs show potential for inducing pancreatic beta cell toxicity.
- This screening approach can aid in identifying environmental risk factors for type 2 diabetes mellitus.
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