Abstract
Chronic hyperglycemia has been associated with an increased prevalence of pathological conditions including cardiovascular disease, cancer, or various disorders of the immune system. In some cases, these associations may be traced back to a common underlying cause, but more often, hyperglycemia and the disturbance in metabolic balance directly facilitate pathological changes in the regular cellular functions. One such cellular function crucial for every living organism is cell cycle regulation/mitotic activity. Although metabolic challenges have long been recognized to influence cell proliferation, the direct impact of diabetes on cell cycle regulatory elements is a relatively uncharted territory. Among other “nutrient sensing” mechanisms, protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification emerged in recent years as a major contributor to the deleterious effects of hyperglycemia. An increasing amount of evidence suggest that O-GlcNAc may significantly influence the cell cycle and cellular proliferation. In our present review, we summarize the current data available on the direct impact of metabolic changes caused by hyperglycemia in pathological conditions associated with cell cycle disorders. We also review published experimental evidence supporting the hypothesis that O-GlcNAc modification may be one of the missing links between metabolic regulation and cellular proliferation.
Highlights
For living organisms, one of the most basic survival skills is the ability to adjust their metabolism to the available resources
Despite the fact that the main problem of diabetes is that cells do not remove glucose from the blood efficiently, the deleterious effects and diabetic complications are due to elevated intracellular glucose (e.g., 2/3 of the advanced glycation end-products are produced intracellularly) [27]
Β-catenin is usually implicated in FOXO and β-catenin [34]. According to their proposed mechanism, they form a complex and are enhancing cell proliferation as part of the Wnt pathway [95], but its effect on cell cycle regulation is translocated in the nuclei, their transcription activity leading to slower proliferation
Summary
Tamás Nagy 1, * , Viktória Fisi 1 , Dorottya Frank 2 , Emese Kátai 1 , Zsófia Nagy 1 and Attila Miseta 1.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.