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Chronic exposure to arsenic, often through contaminated groundwater, has been associated with Type 2 diabetes in humans, and there are new clues that males may be more susceptible to the disease when exposed.
A new Cornell University study — using lab mice genetically modified with a human gene to shed light on the potential link — revealed that while the male mice exposed to arsenic in drinking water developed diabetes, the female mice did not.
These results would not have been possible without using a mouse model engineered to express a human enzyme for metabolizing arsenic, since normal mice process arsenic much more efficiently than humans and require very high levels of exposure before they become diabetic.
“Our paper lays the foundation for future investigations into the mechanism of how arsenic exposure leads to diabetes, why there are striking male-female differences, and potential therapeutic strategies,” said Praveen Sethupathy, professor of physiological genomics and the study’s senior author.
Endemic levels of arsenic above safe limits in both Bangladesh and Mexico led to studies that showed an association between higher levels of arsenic exposure and Type 2 diabetes. Though these studies had very small sample sizes, they offered clues for further research.
Mice in the study were exposed for a month to doses of arsenic in drinking water that were nonlethal but sufficient to potentially promote Type 2 diabetes. The researchers then examined liver and white adipose tissues that are implicated in diabetes. In the humanized male mice alone, they found increased expression in genes related to insulin resistance. Also, in both liver and white adipose tissues of the humanized male mice, they identified a biomarker called miR-34a, which is highly associated with insulin resistance in Type 2 diabetes and other metabolic diseases.
“This would suggest miR-34a is potentially a way to screen individuals who live in areas that have endemic arsenic levels,” said Jenna Todero, first author of the study and doctoral student in Sethupathy’s lab. “If you have elevated miRNA-34a, you might be at risk for Type 2 diabetes onset or other metabolic dysfunction.”
The study was funded by the Superfund Research Program at the National Institute of Environmental Health Sciences.