Given that insulin plays such a pivotal role in controlling glucose metabolism in our bodies, its levels must be firmly kept in check. Although several messengers have been identified that act to enhance its secretion when our glucose levels are high after a meal, none had been identified that negatively regulate insulin in response to starvation, when our glucose levels are low.
Now, researchers have identified a hormone that dampens the release of insulin during recovery from fasting. This molecule therefore helps ensure that valuable nutrients stay in the blood for a sufficient amount of time to help rebuild deprived tissues. Although further characterization is required, the discovery could possibly open up new treatment avenues for diabetics. The study has been published in Cell Metabolism.
Insulin is an extremely important signaling molecule in the body. It’s secreted by cells in the pancreas when our blood sugar (glucose) rises after we eat a meal. Its job is to promote the absorption of excess glucose from the blood, and also to prevent our body from using fat as an energy source. If we have too little insulin, our blood sugar becomes dangerously high; if we have too much, the opposite happens.
While scientists are clued up on what insulin does, what was less clear is what happens when the body faces famine, and thus a lack of glucose. There must be something which prevents our bodies producing insulin and thus storing the sugar we need to recover. In a bid to find out, Stanford scientists began hunting in fruit flies, which are ideal for genetic research because of their simplicity.
After starving the flies for a day, they found that several genes ramped up their protein expression in response, one of which was responsible for the production of a hormone. To find out more about the job of this candidate, they overexpressed it in flies, which caused them to produce too little insulin. Conversely, when they engineered flies to be unable to produce it, their insulin levels were far too high. Consequently, their blood sugar was abnormally low and they ultimately gained weight. The scientists therefore named this protein limostatin, after the Greek goddess of starvation, Limos.
Next, the researchers scoured databases to see if anything similar existed in humans, which turned out a receptor for a protein called Neuromedin U. This protein is known to play a variety of roles, including the control of appetite and hormone function. Interestingly, it turns out that Neuromedin U is expressed in the stomach, and its receptor is found on insulin-producing cells, called beta cells, in the pancreas.
To tie this slowly unraveling story together, the scientists investigated what this protein does to beta cells in the lab. As anticipated, Neuromedin U prevented the cells from being able to release insulin in response to increasing glucose levels. Although these results are pretty convincing, the icing on the cake came when the researchers identified a human family whose members have a mutation in the Neuromedin U gene. These individuals are obese, diabetic, and have abnormally high insulin levels.
Although this work is in its infancy, 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.
