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Fruit Fly Hormone Offers Clue To Diabetes "Cure"




By controlling a hormone in fruit flies, researchers were able to manipulate levels of sugar in their bodies, opening the way to developing a "cure" that would reduce the need for insulin shots in human diabetics.

The dramatic discovery may also lead to new weight-loss drugs that could, for instance, trick the body into thinking it was exercising.

Neurobiologists at Wake Forest University in the US write about their discovery in a paper published online in July in the journal Genetics.

Principal investigator Erik Johnson, an associate professor of biology, said in a statement this week that although fruit flies obviously look quite different to humans, the two species have similar biophysical and biochemical processes, including those that control sugar.

"Why flies are so simple is that they have approximately 100,000 neurons versus the approximately 11 billion in humans," said Johnson.

For their study, Johnson and colleagues examined how fruit flies (Drosophila) react when their food supply diminishes.

Reduced diet or starvation normally causes them to become hyperactive and buzz around like crazy, looking for food.

The frenzied behavior is driven by the secretion of adipokinetic hormone (AKH), which is the functional equivalent of glucagon in humans. The hormone is released by special cells called AKH cells.

(Glucagon, which is secreted in the human pancreas, does the opposite of insulin, it raises blood sugar levels.)

The raised AKH tells the fruit flies' bodies to release more sugar to drive their frantic search for food. And this goes on until all the energy stores in their bodies are used up in the search for food.

The enzyme that triggers the release of adipokinetic hormone (AKH) is called AMP-activated kinase (AMPK), and it is this that the researchers manipulated in the fruit flies.

They also found that when they switched AMPK off, the AKH cells secreted less AKH which lessened sugar release, and the hyperactive behavior in the fruit flies stopped almost completely: even in the face of starvation.

"Since fruit flies and humans share 30 percent of the same genes and our brains are essentially wired the same way, it suggests that this discovery could inform metabolic research in general and diabetes research specifically," said Johnson.

The team suggest two ways the discovery could be used: to research diabetes, and to develop weight-loss drugs.

Diabetes research on glucagon is difficult because pancreatic cells are not easy to pull apart. The AKH cells in fruit flies offer a valuable model in which to research a potential way to target the pancreatic cells that secrete glucagon. It could lead to a treatment, for instance, that reduces the effect of glucagon, which in turn would lessen the release of sugar into the bloodstream.

If such a treatment were to exist, it would reduce the need for diabetics to inject themselves with insulin.

The discovery could also help develop new weight loss drugs that stimulate AMPK and trick the body into thinking it was exercising, as Johnson explained:

"Exercise stimulates AMP-activated kinase, so manipulation of this molecule may lead to getting the benefits of exercise without exercising."

In an earlier study published in PLoS ONE, the team showed how turning off AMPK caused fruit flies to eat a lot more than normal, become less physically active, and gain weight.

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