Common insecticides might create higher risk for diabetes and metabolic diseases

Common insecticides might create higher risk for diabetes and metabolic diseases
This computer-generated image demonstrates how melatonin (in yellow) and carbaryl, (in light turquoise), a commonly used insecticide, bind directly to the same binding region on the human melatonin receptor.

Synthetic chemicals commonly found in insecticides and garden products bind to the receptors that govern our biological clocks, University at Buffalo researchers have found.

The research suggests that exposure to these insecticides adversely affects melatonin receptor signaling, creating a higher risk for metabolic diseases such as diabetes.

Published online on Dec. 27 in Chemical Research in Toxicology, the research combined a big data approach, using computer modeling on millions of chemicals, with standard wet-laboratory experiments.

It was funded by a grant from the National Institute of Environmental Health Sciences, part of the National Institutes of Health.

Disruptions in human circadian rhythms are known to put people at higher risk for diabetes and other metabolic diseases but the mechanism involved is not well-understood.

The current research focuses on two chemicals, carbaryl, the third most widely used insecticide in the U.S. but which is illegal in several countries, and carbofuran, the most toxic carbamate insecticide, which has been banned for applications on food crops for human consumption since 2009.

It is still used in many countries, including Mexico and traces persist in food, plants and wildlife.

The results suggest that there is a need to assess environmental chemicals for their ability to disrupt circadian activity, something which is not currently being considered by federal regulators.

The UB researchers are developing a rapid bioassay that might be able to assess environmental chemicals for this kind of activity.

The work is part of a larger effort by researchers in the laboratories of Dubocovich and Raj Rajnarayanan, PhD, lead author and assistant professor of pharmacology and toxicology at UB, to develop their Chem2Risk pipeline, combining UB’s expertise in computational biology and melatonin receptor pharmacology.

The UB database contains about four million chemicals reported to have some level of toxicity.

After grouping the chemicals in clusters according to their similarity, they found several with functional groups similar to melatonin.

Using predictive computational modeling and in vitro experiments with cells that express human melatonin receptors, they found that carbamates selectively interact with a melatonin receptor.

That interaction can disrupt melatonin signaling and alter important regulatory processes in the body.

“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,” said Dubocovich, the leading author.

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.

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News source: University of Buffalo. The content is edited for length and style purposes.
Figure legend: This Knowridge.com image is credited to Raj Rajnarayanan, UB.