An insulin-suppressing hormone discovered in fruit flies and humans

© Shutterstock
© Shutterstock
Researchers from the Stanford University School of Medicine discovered in fruit flies and humans, a hormone capable of decreasing production of insulin and preventing its release from cells. Modulating this activity might help to manage certain metabolic disorders such as diabetes.


Insulin, a key player in controlling glucose metabolism

Insulin, a peptide hormone produced by beta cells in the pancreas, regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from the blood to muscles and fat tissue and by causing fat to be stored rather than used as a source of energy.

A molecule first discovered in flies

Limostatin was found after the scientists starve their laboratory fruit flies for one day. Then, they found that several genes ramped up their protein expression in response, one of which was responsible for the production of limostatin. After overexpressing the hormone in the flies, they noticed that they were expressing too little insulin. On the other hand, after engineering them unable to produce the hormone, they found that theses flies had high levels of insulin. The researchers therefore named the hormone limostatin after the Greek goddess of starvation, Limos. This molecule dampens the release of insulin during recovery from starvation and so ensures that important nutrients stay in the blood long enough to rebuild deprived tissues.

Neuromedin U : a similar hormone which might play the same role in humans

After identifying the receptor for limostatin in fruit flies, they tried to find if any human protein resembled it. That led them to the receptor of a protein called Neuromedin U. It’s a neuropeptide produced by the brain which has a variety of functions such as the regulation of blood pressure, bone growth, appetite and hormone release. Given the results of the experiments in fruit flies, they hoped that Neuromedin U might also be important in insulin regulation. They discovered that it is present on insulin-producing beta cells in the pancreas and that it appeared to connect nutrient sensing in the gut with insulin-producing cells elsewhere in the body.

To confirm their theories, the scientists tested the effect of physiological levels of Neuromedin U on human pancreatic beta cells and found that it blocked their ability to secrete insulin in response to increasing glucose levels. Finally, they identified a family whose members have a have a mutation in the Neuromedin U gene. These individuals have early onset obesity and diabetes and abnormally high insulin levels.

Although the work is in its early stages, the researchers are hopeful that in the future, it might be possible to modulate Neuromedin U in order to manage certain metabolic conditions, such as diabetes.