Glucose Metabolism in Glia and Neurons

Introduction of Glucose Metabolism

Neurons and glia are important cellular components for both the central nervous system (CNS) and peripheral nervous system (PNS) to perform a series of functions. As the non-neuronal cells, glia can form myelin, maintain homeostasis, regulate development, as well as recovery after neuronal injury. Recent studies have shown that the brain is an organ of unusually high metabolic demand. It only accounts for 2% of the body's volume but consumes almost 20% of the total oxygen and glucose in the human body. Brain glucose is mostly consumed by astrocytes and oligodendrocytes. The glucose metabolites will be used by neurons to meet their energy needs. A considerable proportion of glucose in the brain is metabolized to lactate and lactate has been served as the preferred energy metabolite for multiple neuronal functions. Acetate, as a two-carbon intermediate in metabolism, is also an alternative fuel for the brain.

Fig.1 Glia-neuron metabolic interactions in the CNS are most likely mediated by monocarboxylate and glucose transporters (MCTs and GLUTs, respectively). (Jha, 2018)

Glucose Transporters for Glucose Metabolism

Glucose is the primary energy source for the nervous system, and it is almost fully oxidized in the brain. Glucose transporter can ensure the effective uptake of glucose by nerve cells and play an important role in the nervous system.

GLUT family has been served as the major facilitator superfamily of membrane transporters. GLUT 1-4 are important glucose transporters with distinct regulatory and kinetic properties. For example, GLUT3 expressed by neurons allows the direct import of glucose into neurons. GLUT1 helps glucose pass through the blood-brain barrier from the blood to the brain. The expression and function of both GLUT3 and GLUT1 are highly regulated by transcriptional and post-transcriptional processes in the brain.

Fig.2 Differential expression of monocarboxylate and glucose transporters (MCTs and GLUTs, respectively) in peripheral nerve. (Jha, 2018)

Diseases Associated with Glucose Metabolism

Recent research has shown that disorders of glucose metabolism can lead to many different neurological diseases, including peripheral neuropathies, neuroinflammation, neurodegenerative disorders, and psychiatric disorders. Future research focused on metabolic transporters would broaden our understanding of CNS and PNS physiology and pathology, as well as provide novel therapeutic options for patients with neurological diseases.

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Reference

1. Jha, M.; Morrison, B. Glia-neuron energy metabolism in health and diseases: new insights into the role of nervous system metabolic transporters. Experimental neurology. 2018, 309: 23-31.