The Role of Natural Factors that Optimize Redox Status in Combating Type 2 Diabetes

Abstract

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

The link between theANPEPgene and type 2 diabetes mellitus may be mediated by the disruption of glutathione metabolism and redox homeostasis

“…The same can be said for ANPEP, whose expression level is increased both in the plasma and beta cells of the pancreatic islets in patients with type 2 diabetes [23,50,96]. The main assumption is that increased expression of amino acid and peptide metabolism enzymes is required to provide amino acid precursors for the biosynthesis of glutathione, the deficit of which is considered a primary cause of type 2 diabetes [21,31,35].…”

“…Third, decreased glutathione levels are closely correlated with the pathological conditions found in T2D, and replenishment of glutathione deficiency improves them. These pathological changes include oxidative stress and mitochondrial dysfunction [31,32,[35][36][37], β-cell dedifferentiation and failure [38], impaired glucose tolerance, insulin secretion [39][40][41] and sensitivity [42,43]. In addition, the depletion of endogenous glutathione is correlated with increased blood glucose levels and contributes to the complications of type 2 diabetes [33,34,38].…”