The importance of glutaredoxin for diabetes and its complications

Diabetes mellitus is a non-communicable metabolic disease characterized by chronic hyperglycemia caused by beta-cell failure. Diabetic complications affect the vascular system, causing macroangiopathy and microangiopathy, which contributes to significantly increased morbidity and mortality. The increasing incidence and prevalence of diabetes represents a major global health burden. There are no viable strategies for preserving beta cells available in routine clinical practice. Therefore, patients rely on antidiabetic drugs and extracorporeal insulin administration. Glutaredoxins (Grxs) are members of the ubiquitously expressed and highly conserved thioredoxin family of proteins. They have specific functions in redox-mediated signaling, iron homeostasis, iron-sulfur (FeS) protein biosynthesis, and regulation of cell proliferation, survival, and function. The involvement of Grx in chronic diseases has been a research topic for decades, and Grx have been suggested as therapeutic targets. Little is known about their role in diabetes and its complications. Therefore, this review summarizes the available literature on the importance of Her-Grx in diabetes and its complications. In conclusion, Grxs are differentially expressed in the endocrine pancreas and tissues affected by diabetic complications, such as the heart, kidneys, eyes, and vasculature. They are involved in several pathways essential for insulin signaling, metabolic inflammation, glucose and fatty acid uptake and processing, cell survival, and iron and mitochondrial metabolism. Most studies have described significant changes in glutaredoxin expression and/or activity in response to diabetic metabolism.

Generally, decreased Grx levels are associated with oxidative stress, cell damage, and even cell death. The induced overexpression is considered a potential part of the cellular stress response, countering oxidative stress and beneficially affecting cellular functions such as insulin secretion, cytokine expression, and enzyme activity.