University at Buffalo biologists recently discovered that toxic chemicals commonly found in insecticides have the ability to change the way our biological clocks function. The researchers believe that they have uncovered the previously unknown mechanism by which insecticides put people at higher risk for metabolic diseases like diabetes.
The team, led by Marina Popevska-Gorevski, used predictive computational modeling on millions of chemicals and in-vitro experiments with cells that express human melatonin receptors, combining big data techniques with standard wet-lab approaches.
They focused on two carbamate-based chemicals commonly found in insecticides and garden products, carbaryl and carbofuran. Carbaryl, which is illegal in several countries, is the third most widely used insecticide in the United States. In 2009, the Environmental Protection Agency banned carbofuran, the most toxic carbamate, from application on food crops. However, many countries, including Mexico, still use carbofuran.
The results are part of a larger project that Margarita Dubocovich and her team at the University at Buffalo (UB) are currently working on. They have developed a bioassay, called Chem2Risk, capable of predicting the risk factor of all types of chemicals. She and her colleagues have developed a database containing approximately four million chemicals capable of causing human harm with varying levels of toxicity.
“Our approach seamlessly integrates the screening of environmental chemicals through computer simulation, in vitro and in vivo techniques to gauge the risk these chemicals present for various disease end points,” Raj Rajnarayanan, lead author and assistant professor of pharmacology and toxicology at UB, said in a press release.
According to Rajnarayanan, of those four million chemicals, they were able to quickly identify hundreds of thousands of compounds with readily available chemical structures. They then grouped the chemicals according to their structural similarities. From there they found that several groups had structures similar to that of melatonin.
“By directly interacting with melatonin receptors in the brain and peripheral tissues, environmental chemicals, such as carbaryl, may disrupt key physiological processes leading to misaligned circadian rhythms, sleep patterns, and altered metabolic functions increasing the risk for chronic diseases such as diabetes and metabolic disorders,” Dubocovich, SUNY distinguished professor in the Department of Pharmacology and Toxicology, said.
For example, she explained, there is a fine balance between the release of insulin and glucose in the pancreas at very specific times of day, but if that balance becomes disrupted over a long period of time, there is a higher risk of developing diabetes.
According to Popovska-Gorevski both insecticides were built like melatonin in structure and both were able to bind tightly and accurately to the melatonin receptor, potentially affecting how the body is able to produce insulin and regulate glucose levels.
“That means that exposure to them could put people at higher risk for diabetes and also affect sleeping patterns,” Popovska-Gorevski said.
“This is the first report demonstrating how environmental chemicals found in household products interact with human melatonin receptors,” said Dubocovich, who is also senior associate dean for diversity and inclusion in the Jacobs School of Medicine and Biomedical Sciences at UB.
“No one was thinking that the melatonin system was affected by these compounds, but that’s what our research shows,” she said.
The results suggest the federal government may need to change their approach in assessing the effect environmental factors have on the human circadian rhythm.
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