Finding that Melatonin, a hormone mostly known from sleep research and an active ingredient used in sedatives, was involved in diabetes came as a surprise to the scientists.
- Completely unexpected and very exciting, was the comment of Hindrik Mulder, leader of one of the two research groups.
The connection was discovered in two large genetic studies that compared more than 18 000 healthy individuals, with diabetic individuals. It was found that a variant of the melatonin receptor gene was more common among those that had diabetes.
- Individuals with this variant had elevated blood glucose levels and impaired insulin secretion already when these studies started 25 years ago. It makes sense that a larger number of them have eventually developed diabetes, says Valeriya Lyssenko, who was responsible for the genetic analysis.
The risk variant is common: approximately 30 percent of the population have it.
The next step was to investigate by what mechanism the gene variant affects the risk of getting diabetes. Studies performed on insulin producing cells showed that melatonin decreases the ability of the cells to secrete insulin.
- We have discovered that the gene variant most likely increases the amount of the melatonin receptor on the cell surface. This makes the cells more sensitive to melatonin, which reduces their capacity to release insulin. Because the receptor is located on the cell surface, it could be possible to develop a drug that blocks the receptor and counteracts the inhibiting effect of the melatonin, says Cecilia Nagorny, who has performed the analyses on the insulin producing cells.
The melatonin level in the body is affected by light. In the dark hours of the night the level is high whereas the level drops during the day. It is also well known that melatonin affects the circadian rhythm.
- One possible explanation for the diabetes connection is that the high melatonin levels in the night should limit the amount of insulin produced during sleep when the requirement is low. By day, the melatonin level decreases, which would normally allow a higher insulin secretion, but in individuals with this risk variant insulin secretion is constantly inhibited, says Hindrik Mulder.
The scientists at LUDC are currently awaiting knockout mice in which the melatonin receptors have been deleted. The mice come from sleep researchers in the US but at LUDC, focus is on the insulin producing cell.
Link to the article in Nature Genetics: A common variant in the melatonin receptor gene (MTNR1B) is associated with increased risk of future type 2 diabetes and impaired early insulin secretion
For more information:
Hindrik Mulder, research group leader for cell analyses;
040 – 39 10 23, 070 - 292 69 28, Hindrik [dot] Mulder [at] med [dot] lu [dot] se (Hindrik[dot]Mulder[at]med[dot]lu[dot]se)
Leif Groop, research group leader for genetic analyses;
040 – 39 12 02, 070 – 591 25 48, Leif [dot] Groop [at] med [dot] lu [dot] se (Leif[dot]Groop[at]med[dot]lu[dot]se)