Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? - PubMed (original) (raw)

Review

Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models?

Jennalynn Styskal et al. Free Radic Biol Med. 2012.

Abstract

The development of metabolic dysfunctions like diabetes and insulin resistance in mammals is regulated by a myriad of factors. Oxidative stress seems to play a central role in this process as recent evidence shows a general increase in oxidative damage and a decrease in oxidative defense associated with several metabolic diseases. These changes in oxidative stress can be directly correlated with increased fat accumulation, obesity, and consumption of high-calorie/high-fat diets. Modulation of oxidant protection through either genetic mutation or treatment with antioxidants can significantly alter oxidative stress resistance and accumulation of oxidative damage in laboratory rodents. Antioxidant mutant mice have previously been utilized to examine the role of oxidative stress in other disease models, but have been relatively unexplored as models to study the regulation of glucose metabolism. In this review, we will discuss the evidence for oxidative stress as a primary mechanism linking obesity and metabolic disorders and whether alteration of antioxidant status in laboratory rodents can significantly alter the development of insulin resistance or diabetes.

PubMed Disclaimer

Figures

Figure 1

Modulation of oxidative stress is a central process in the development of obesity-induced insulin resistance. Increasing fat accumulation (Obesity) can generate oxidative stress in multiple ways, including increased mitochondria-derived ROS, increased activity of NADPH oxidases, decreased antioxidant expression, and promotion of a pro-inflammatory environment. By activating stress responsive pathways like JNK, increasing cytokine expression, or perhaps through direct oxidative damage of signaling proteins, this oxidative stress can lead to decreased insulin response of the insulin signaling pathway (right). These data suggest that reduction of oxidative stress may be a viable therapeutic or preventative treatment for insulin resistance.

References

1. NIH. National Diabetes Statistics. National Institutes of Health; 2007.
1. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care. 1992;15:318–368. - PubMed
1. Pessin JE, Saltiel AR. Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest. 2000;106:165–169. - PMC - PubMed
1. Kraegen EW, Clark PW, Jenkins AB, Daley EA, Chisholm DJ, et al. Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes. 1991;40:1397–1403. - PubMed
1. Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem. 1997;272:20313–20316. - PubMed

Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? - PubMed (original) (raw)