|
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. |