Glucose Homeostasis: From Consumption to Complete Metabolic Pathways

Abstract

A complex and precise set of regulatory mechanisms control the concentration of glucose in our blood. This balanced glucose homeostasis is relevant for successful cellular construction, energy provision, and redox balancing. The blood typically contains 5 grams of glucose. To avoid hypoglycemia, cells should have instantaneous access to extra-cellular glucose sources, both due to the secretion of insulin, causing the release of extra glucose, and the glycolysis inhibitor hormone glucagon. This availability of glucose for skeletal muscles, the brain, and cells lacking mitochondrion forms the cornerstone of the evolution of the auxiliary functions of locomotion and warm-bloodedness. But glucose, if prevalent in the extra-cellular environment, might also trigger oxidative stress and, together with it, cell senescence and carcinogenesis. However, the glucose-induced protective response might fail, especially in cells and tissues prone to tumor initiation. Such dysfunctions on the background of active glycolysis bear the hallmarks of the Warburg effect. Hyperglycemia triggered by the modern diet, possibly the main inducer of the Warburg effect, significantly aggravates the risk of many diseases, including cancer and neurodegenerative ones.