Glucose metabolism in the brain: An update

The human brain uses glucose as the primary source of energy for its physiological functions. Alteration of blood glucose levels leads to hypo/hyperglycemic conditions. Consequently, the brain undergoes dysregulation of glucose metabolism which is further associated with various pathological disorders causing cognitive impairment and loss of critical brain functions. Glucose metabolism is connected with multiple other metabolic pathways in order to generate adequate energy for neuronal cells to carry out their functions. Therefore, glucose homeostasis plays a prominent role in the maintenance of healthy brain physiology. Glucose homeostasis is regulated by different factors including glucose transporters, hypothalamus, neuron-astrocyte crosstalk, and endocrine hormones. Further, glucose not only acts as a source of energy for the brain, but also partakes in significant regulatory functions, including acting as a substrate for the precursors of neurotransmitter synthesis, maintenance of ionic concentration gradient across the membrane, promoting neuroplasticity, management of oxidative stress, learning, and memory. Ultimately, dysregulation of glucose metabolism is linked to various pathological disorders of the brain including hyper/hypoglycemia, diabetic retinopathy, oxidative stress, neurodegeneration, apoptosis, autophagy, and cognitive dysfunction. The main purpose of this chapter is to provide recent updates on glucose metabolism of the central nervous system (brain and eye) and the consequences of its dysregulation.