Discovering the Connection Between Environmental Arsenic Exposure and Type 2 Diabetes
Dec. 9, 2019
Dr. Donna Zhang, professor of pharmacology and toxicology at the College of Pharmacy, and Dr. Matthew Dodson, UA SRP Trainee and post-doctoral research associate, presented their research on the connection between arsenic exposure and Type 2 diabetes at the Society of Toxicology annual meeting in March 2019. Dr. Zhang, one of the leading experts on the subject, and her laboratory study the mechanism by which arsenic promotes disease.
Arsenic occurs naturally in many areas of the world, often in the water supply. Very low levels are not a risk, but concentrations above 10 micrograms per liter are unsafe for humans, according to the World Health Organization. “We know there is a link between exposure to arsenic and diseases such as cancer and Type 2 diabetes, but the mechanism is not well understood,” says Dr. Zhang. “Our work focuses on revealing that mechanism. If we can do that, then we can find a way to prevent or slow down the disease.”
Dr. Dodson has been working in Dr. Zhang’s lab for four years, leading experiments using mouse models to examine how chronic exposure to arsenic causes genetic changes and how those changes are linked to disease development.
The team looked at the role of prolonged changes in a set of RNA molecules called the Nrf2 transcriptome. Nrf2 is a master regulator of redox, protein, and metabolic homeostasis. In a normal cell, it is activated intermittently. In a cancer cell or a cell where autophagy is not working properly, Nrf2 is activated for extended periods or continuously. The latter is what happens when a person is exposed to arsenic over a long period of time. When autophagy stops working, Nrf2 is not activated in the normal way, and this, in turn, promotes disease.
Dr. Zhang’s lab is working with QIAGEN Genomic Services to help understand Nrf2 regulation and the role of Nrf2 in diabetic disease. This company has the tools to screen massive data sets to assess gene expression with high level of accuracy.
“The insights we gained through QIAGEN’s analysis point the way to a possible therapeutic target for disease intervention,” says Dr. Dodson. “We could look for a way to activate autophagy so that it works normally, or ways to inhibit Nrf2.”
The next stage would be to move from animal models to human models. “This is the very beginning of a giant project. We have so much data. We need to dig deeper to understand the mechanism,” says Dr. Zhang. “People don’t realize how widespread arsenic is. That is a real danger. If we can figure out the pathways that lead to diabetes, we can develop treatment and even prevent it from causing the disease.”