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Glucose Metabolism in the Brain, Volume 51 (International Review of Neurobiology.)

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Glucose is an essential energy source for the adult human brain. When blood glucose levels fall by half from a normal fasting value (to about 2–3 mM), there is some cognitive impairment and, at glucose levels below 1 mM, mental confusion is evident and coma may result from sustained glucose deprivation. Recent studies have demonstrated that optimum neuronal function and even cell survival are determined by the efficiency of energy metabolism. Thus, cells that use glucose as their primary energy source are less susceptible to stress and harmful conditions than cells that use other energy sources or that exhibit higher rates of glycolysis. Although our knowledge about the critical role of glucose metabolism in the maintenance of high level brain function has grown considerably in recent years, the various factors that regulate glucose uptake and utilization in the CNS are not well understood. Moreover, the brain must regulate the relative use of glucose, glutamine, and ketone bodies for energy under normal circumstances and especially during development and aging.

The regulation of glucose metabolism in humans is a complex process that proceeds via a two-way street connecting the brain and peripheral tissues. The CNS monitors glucose levels and exerts indirect control over both the utilization and production of glucose via hormone secretion and innervation. Peripheral tissues, including muscle, fat, pancreas, and liver, are responsible for direct control over the transport, synthesis, storage, and metabolism of glucose. Specific signals are conveyed back to the brain and nonspecific information, such as the overall metabolic state, can produce a significant impact on brain function. For example, injury to brain tissue in stroke is much more extensive in patients with hyperglycemia or diabetes as compared to patients with normal levels of blood glucose. Similarly, tardive dyskinesia, a serious movement disorder induced by neuroleptic drugs, occurs more frequently in patients with elevated blood glucose levels. Furthermore, a number of neurologic and psychiatric conditions are associated with alternations in energy metabolism in both the brain and peripheral tissues. Research efforts aimed at providing insights into the relationship between glucose metabolism and brain dysfunction should be a high priority.
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