Research Reveals Blood Sugar's Effect on Wakefulness
Finding could lead to treatments for problems like sleep disorders and obesity
WEDNESDAY, May 31, 2006 (HealthDay News) -- Ever notice that hunger can sharpen your senses, while a full, satisfying meal leaves you yearning for a nap?
The key to this response is the simple sugar glucose, and British researchers have discovered how it works its neural magic.
In experiments with mice, the researchers determined how glucose blocks neurons -- brain cells -- that regulate wakefulness. They found that a class of potassium ion channels made up of proteins in the cell membrane affects the cells' responses by controlling the amount of potassium getting into the cells.
Then they wanted to find out how glucose inhibits a particular class of glucose-sensing neurons that produce tiny proteins called orexins, which regulate states of consciousness.
"The firing of consciousness-regulating brain cells is sensitive to changes in glucose that occur between normal meals," said lead researcher Denis Burdakov, a research fellow at the University of Manchester. "Now we know how glucose can stop neurons from firing, something which eluded neuroscientists for the last 30 years."
The findings appear in the June 1 issue of the journal Neuron.
Burdakov said it was known that glucose inhibits the activity of orexin neurons; malfunction of these cells can lead to narcolepsy and obesity. "Recently, it was discovered that these brain cells promote wakefulness and when lost, lead to narcolepsy. But how glucose does this was unknown," he added.
In its experiments, Burdakov's team used engineered mice to produce a fluorescent protein only in orexin neurons. This allowed the researchers to isolate the neurons in brain slices from the mice and perform precise biochemical and electrophysiological studies to explore how glucose acted on those neurons.
Then the researchers did experiments exposing the neurons to the subtle changes in glucose levels known to occur in daily cycles of hunger and eating. They found that activation of a type of potassium in the membrane of orexin neurons is responsible for glucose's inhibitory action.
"This previously unknown mechanism of glucose-sensing is so sensitive, it can detect minute changes in glucose levels that occur, for example, between normal breakfast and lunch," Burdakov said.
It seems that the activity of orexin neurons, which regulate appetite and reward feelings, as well as wakefulness, can be controlled by normal, daily changes in brain glucose levels, Burdakov said. "This may provide a candidate explanation for after-meal sleepiness and for why it is difficult to sleep when hungry," he said.
The finding may also have implications for designing new drugs that target this potassium channel, Burdakov said. "This could be a treatment for disorders that involve orexin neurons and/or brain glucose sensing, such as disorders of sleep and body weight like obesity, anorexia, diabetes and narcolepsy," he said.
Christopher M. Sinton, an assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, said, "This [glucose] mechanism is unexpected because it is unusual, and the paper is a careful and exceptional description of its discovery."
"Perhaps more importantly, however, we now know why orexin cells can be so exquisitely sensitive to very small changes in circulating glucose levels, and also how they respond very rapidly to these changes," Sinton said. "Hence the activity of orexin cells will be increased even by the relatively small changes in glucose that occur for short periods between meals."
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