Oxidative stress means that, at the cellular level, there is an excess of oxidants that overcome the body's antioxidant capabilities to deal with them. These oxidants are often called "free radicals" or "free radical species," because they are chemically unstable and can react with other molecules. Oxidants include both "reactive oxygen species" and "reactive nitrogen species." They can be produced both by the body itself, and as a result of environmental exposures. Scientists have confirmed that oxidative stress is involved in the development of some diseases, but exactly how it is involved is not yet known (Franco and Panayiotidis 2009).
Beta cells are highly sensitive to oxidative stress. Both reactive oxygen species and reactive nitrogen species are likely to be involved in beta cell destruction in type 1 diabetes (Lenzen 2008a). Van Dyke et al. (2010) hypothesize that oxidative/nitrosative stress can trigger type 1 diabetes, and have prevented toxin-induced diabetes in rats with an antioxidant. Alloxan, one of the drugs used to induce insulin-dependent diabetes in lab animals, is thought to cause diabetes via a mechanism that involves reactive oxygen species (Lenzen 2008b). (See the beta cell stress page for more information on beta cells.) Treatment with testosterone increases the susceptibility of some types of cells to oxidative stress (Prudova et al. 2007). Unlike other autoimmune diseases, type 1 diabetes is not more common in females than males (see the gender and age page). Perhaps testosterone can increase the susceptibility of beta cells to oxidative stress, contributing to a higher than expected incidence in males.
Environmental factors can not only induce oxidative stress, but can also activate the body's own repair mechanisms to counteract oxidative stress. The resulting cell death or cell survival can depend on the length, intensity, and type of environmental exposure (Franco et al. 2009). In other words, not all oxidative stress may be "bad."
And, not all anti-oxidants may be "good." There is some animal evidence that anti-oxidants can increase insulin resistance. When researchers gave certain mice an anti-oxidant, they were more likely to become insulin resistant (Loh et al. 2009). These findings may help to explain why anti-oxidants have not been found to be protective against type 1 diabetes (see the nutrition page). On the other hand, reactive oxygen species can trigger insulin resistance in animals as well (Houstis et al. 2007).
Many toxic chemicals can generate reactive oxygen and nitrogen species (Lenzen 2008a). A number of environmental contaminants are known to induce oxidative stress as well as apoptosis (programmed cell death). Apoptosis of beta cells is the main cause of beta cell death at the onset of type 1 diabetes (Cnop et al. 2005). Franco et al. (2009) review how many contaminants, including heavy metals, arsenic, some air pollutants, some pesticides, and some persistent organic pollutants, affect apoptosis via oxidative stress.
As an air pollutant, particulate matter carries contaminants that are capable of triggering the production of free radicals, and may affect organs that are sensitive to oxidative stress (MohanKumar et al. 2008). Hathout et al. (2006) propose that the oxidative effects of air pollutants ozone and sulfate (SO4) may contribute to the development of type 1 diabetes.
In genetically susceptible mice, exposure to tricholorethylene at levels found in the environment leads to oxidative and nitrosative stress, and is associated with the induction and exacerbation of autoimmunity (Wang et al. 2007). High doses of N-nitroso compounds (see the nitrate/nitrite page) can cause diabetes via the generation of free radicals that damage beta cells. The effect of lower levels of exposure is less clear (Kostraba et al. 1992).
The bottom lineOxidative stress may be involved in the development of type 1 diabetes. Whether the ability of environmental contaminants to produce oxidative stress would lead to the development of type 1 diabetes is not known, but deserves further study. |