The role of Reactive oxygen species (ROS) in the progression of Type 2 diabetes
Type 2 diabetes is the most prevalent metabolic disease currently known to man. Its hallmarks are pancreatic beta-cell dysfunction and insulin resistance. The Reactive Oxygen Species (ROS) is a little understood factor as far as the progression of Type 2 diabetes is concerned, and therefore, in this article, I will shed some light on what it is and the effect it has on this chronic disease.
ROS is a type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell. A buildup of reactive oxygen species in cells may cause damage to DNA, RNA, and proteins, and may cause cell death. Reactive oxygen species are free radicals, also called oxygen radicals.
Traditionally, ROS have been thought to be generally harmful to biological systems producing useless by-products of respiratory metabolism in mitochondria. Growing evidence shows that, in many instances, ROS is not harmful or useless, but rather an essential element for certain biological responses. It’s been demonstrated that ROS are critical factors in how cells normally send signals and regulate some insulin secretions. Excessive or sustained ROS production can disturb the way cellular parts function, such as DNA, protein, or lipids.
As discussed above, ROS action is generally beneficial. Under diabetic conditions, chronic hyperglycemia and consequent augmentation of reactive oxygen species (ROS) deteriorate beta-cell function and escalate insulin resistance leading to an aggravation of the type 2 diabetes. Additionally, chronic hyperglycemia and ROS are also involved in the development of atherosclerosis which is often observed under diabetic conditions.
Such disturbances contribute to the formation and progression of various diseases, including diabetes. To counteract these insults, most cells, including β-cells, have intricate mechanisms of defense against ROS toxicity often resulting in oxidative stress.
In response to oxidative stress, activation of certain proteins (Nrf2) dramatically increase the activation of antioxidant enzymes thus increasing the ability to remove the extra oxygen from the cells. This removal of abundant oxygen from the cells is critically important for returning to homeostasis or state of rest and protects cells from irreversible oxidative damage.
Diabetes mellitus (DM) is an independent risk factor of heart failure. The Framingham Heart Study reported that the frequency of heart failure is 2-fold higher in male diabetics and 5-fold higher in female diabetics than in age-matched control subjects. An increase in reactive oxygen species (ROS) has been regarded as a dominant mechanism of cardiac dysfunction in patients with DM. ROS are important intracellular signaling molecules and mediate various cellular functions, including activation of transcriptional factors, protein kinases, and ion channels; however, high levels of ROS are detrimental to cardiomyocytes.
It can therefore be said that Reactive oxygen species (ROS) are the main facilitators of cardiovascular complications in diabetes mellitus (DM). Emerging evidence shows that mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are dominant mechanisms of ROS production in the diabetic heart.
In physiological conditions, ROS levels are appropriately controlled by antioxidant enzymes to minimize cellular damage from oxidation. Oxidative stress occurs when ROS production overwhelms antioxidant capacity in pathological conditions. It is apparent that ROS production and oxidative stress are increased in the diabetic heart, and oxidative stress induces various cardiovascular complications including cardiac dysfunction which is facilitated by inflammation, apoptosis, and fibrosis. The rise in the ROS level in the diabetic heart is brought about by multiple mechanisms making it a complex problem.
ROS are induced under diabetic conditions, which are possibly involved in the progression of pancreatic cell dysfunction and insulin resistance found in type 2 diabetes. Suppression of ROS in obese type 2 diabetic mice restores cell function and insulin sensitivity, leading to amelioration of glucose intolerance. In addition, ROS are involved in the progression of atherosclerosis which is often observed as the way blood clots and fat build up in the arteries under diabetic conditions.
Taken together, it is likely that ROS are closely associated with the development of type 2 diabetes and atherosclerosis, but at present, several clinical trials with antioxidants show only a little effect, if any, on the progression of type 2 diabetes. Future therapy might look into the suppression of ROS and infusion of stronger and more appropriate antioxidants as a way of exerting some beneficial effects against the development of type 2 diabetes and atherosclerosis.