Researchers have discovered that increasing levels of the sleep hormone melatonin reduces the ability of insulin-producing cells to release insulin. Also, they found the effect is stronger in people who carry a particular gene variant that is linked to higher risk for type 2 diabetes.
The study, led by Lund University in Sweden, is published in the journal Cell Metabolism.
The findings mark the culmination of work that goes back to 2009, when Lund researchers showed that a variant of the gene that codes for the protein known as melatonin receptor 1B (MTNR1B) increases the risk for type 2 diabetes.
Melatonin is a hormone that helps to maintain our day-night cycle, or circadian rhythm, by regulating other hormones. The amount of melatonin in our blood varies through the day. It is affected by light and peaks during the darkest time, at night.
Insulin is a hormone that regulates blood sugar levels. It is produced and released by the beta cells of the pancreas, in response to spikes in blood sugar, such as during digestion.
In type 2 diabetes, which accounts for nearly 90 percent of diabetes, the body either does not produce enough insulin, or cells become less effective at responding to it, which increases demand on the beta cells to produce more. Both of these result in increased levels of blood sugar, which eventually causes serious damage to organs.
In the new study, the researchers worked with lab-cultured beta cells and mice to show that insulin-producing cells respond to increased levels of melatonin by reducing the amount of insulin they release. These signals are conveyed to them via the MTNR1B melatonin receptor proteins on their cell surfaces.
The researchers also showed mice with disrupted MTNR1B receptors produced more insulin.
Melatonin reduction of insulin stronger in risk-gene carriers
Finally, the team demonstrated that a gene variant carried by around a third of the population increases the amount of MTNR1B protein on the surface of insulin-producing cells. This makes the cells more sensitive to the effects of melatonin, which results in less insulin.
For this last part of the study, the team recruited 23 healthy carriers of the gene variant and 22 healthy non-carriers. All participants were around the same age, had the same body mass index (BMI), and showed no differences in family history of diabetes.
For 3 months, the participants took 4 milligrams of melatonin before they went to bed at night. The researchers compared blood sugar and insulin levels taken at the start and end of the treatment period.
After 3 months of melatonin treatment, all participants had higher levels of blood sugar. However, these were especially higher in the carriers of the risk gene, who also showed lower levels of insulin secretion.
The researchers note that people who work overnight shifts are more prone to metabolic diseases like type 2 diabetes.
Senior investigator Hindrik Mulder, a professor specializing in molecular metabolism at Lund's Diabetes Center, says their findings could explain why the risk of developing type 2 diabetes is higher in people who work overnight or who have sleeping disorders.
He also suggests melatonin's apparently stronger effect on people who carry the risk gene could explain why they are also at increased risk of developing type 2 diabetes.
"It is perhaps therefore less suitable for carriers of the risk gene to work overnight shifts, as the level of melatonin will probably increase at the same time as the effects of the increase are enhanced. There is still no scientific support for this theory, but it ought to be studied in the future, on the basis of our new findings."
Prof. Hindrik Mulder
The researchers note that theirs is one of the first studies of its kind in type 2 diabetes research where participants have been recruited based on their genetic makeup.