Molecular mechanisms of ROS production and oxidative stress in diabetes

Abstract

Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and tissues, is a result of over production of oxidative-free radicals and associated reactive oxygen species (ROS). One outcome of excessive levels of ROS is the modification of the structure and function of cellular proteins and lipids, leading to cellular dysfunction including impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity, immune activation and inflammation. Nutritional stress, such as that caused by excess high-fat and/or carbohydrate diets, promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation and decreased antioxidant status. In obesity, chronic oxidative stress and associated inflammation are the underlying factors that lead to the development of pathologies such as insulin resistance, dysregulated pathways of metabolism, diabetes and cardiovascular disease through impaired signalling and metabolism resulting in dysfunction to insulin secretion, insulin action and immune responses. However, exercise may counter excessive levels of oxidative stress and thus improve metabolic and inflammatory outcomes. In the present article, we review the cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action, from the point of view of possible application of novel diabetic therapies based on redox regulation.

Inverse associations of HDL cholesterol and oxidized HDL with d-dimer in patients with type 2 diabetes mellitus

“…However, it remains to be determined how blood lipids are related to coagulation and fibrinolysis activities in patients with diabetes. Although diabetes causes increased oxidative stress [2], it is not known whether oxidized lipoproteins such as oxidized LDL (ox-LDL) and oxidized HDL (ox-HDL) are associated with changes in blood coagulation and fibrinolysis in diabetes patients. The purpose of this study was therefore to clarify the relationships of blood lipids and oxidized lipoproteins with d-dimer, a coagulation-fibrinolysis marker, in patients with diabetes.…”

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

“…This occurs especially at complexes I and III. Similarly, metabolic activity, especially during enzymatic processes, cause the production of damaging ROS (Figure 2) [113]. ROS/RNS are obviously involved in the molecular damage that precedes a mutation and cancer initiation.…”

Daily Intake of Grape Powder Prevents the Progression of Kidney Disease in Obese Type 2 Diabetic ZSF1 Rats

“…, hypoxia and immunologic stimuli) [48,49,50] and the loss of antioxidant defense system that includes enzymes (e.g., SOD, CAT and GSH-Px) and small molecular antioxidant scavengers (e.g., vitamin E, N -acetylcysteine and α-lipoic acid) [51,52]. The oxidative stress or ROS causes cellular damage by reacting with and/or denaturing cellular macromolecules including lipid, protein and nucleic acids, and/or even mediating or activating intracellular death signaling pathways [53], which plays an important role in the pathogenesis and progression of diabetes, fatty liver disease and their associated CKD including DN [52,54,55,56]. Grape products are rich in antioxidant chemicals, such as phenolic, flavonoid, and anthocyanidin [57,58,59], and exhibit anti-oxidative activities in both humans and animals [37,60,61].…”