Home‎ > ‎Potential Mechanisms‎ > ‎

Oxidative Stress

Oxidative Stress
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).

People with type 1 diabetes have elevated levels of oxidative stress, which may play a role in the development of complications such as cardiovascular disease (Tran et al. 2012).

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 chemicals 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.)

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). Reactive oxygen species can trigger insulin resistance in animals as well (Houstis et al. 2006). Indeed, oxidative levels plays a role in metabolism and metabolic diseases such as type 2 diabetes as well (Nocito et al. 2015).
 
soccer

Oxidative stress is not always "bad." Exercise, for example, can induce oxidative stress.
Many toxic chemicals can generate reactive oxygen and nitrogen species (Lenzen 2008a). A number of environmental chemicals 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 chemicals, including heavy metals, arsenic, some air pollutants, some pesticides, and some persistent organic pollutants, affect apoptosis via oxidative stress. Gassman (2017) reviews the literature on how BPA may contribute to the development of human diseases (including diabetes and obesity) via oxidative stress.
 
As an air pollutant, particulate matter carries chemicals 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).

Oxidative stress may also play a role in other types of diabetes, including gestational diabetes. Women with gestational diabetes are less able to compensate for oxidative stress than women without gestational diabetes (Zhu et al. 2015).

In people with diabetes, glucose levels influence oxidative stress levels. Fluctuations in glucose levels, common in type 1, may even be more important that high glucose levels in triggering oxidative stress (Meng et al. 2015).

The bottom line

Oxidative stress may be involved in the development of type 1 diabetes. Whether the ability of environmental chemicals to produce oxidative stress would lead to the development of type 1 diabetes is not known, but deserves further study.

References

To see these and additional articles relating to oxidative stress and diabetes, as well as articles on the numerous environmental factors that can trigger or influence oxidative stress, see my PubMed collection, Oxidative stress.