A predisposition to have a pancreas that’s more sensitive to the insulin-inhibiting effects of melatonin, may be present in up to 30 percent of the population, a new study suggests. Individuals with this increased sensitivity carry a slightly altered melatonin receptor gene that is a known risk factor for type 2 diabetes.
Large-scale studies have found more than 100 genes associated with an increased risk of developing type 2 diabetes. On the list of risk factors is a single change to the melatonin receptor gene MTNR1B, found in 30 percent of the population.
It is known that the MTNRIB receptor makes cells sensitive to melatonin, but Hindrik Mulder of Lund University in Sweden and Leif Groop, of Lund University and the University of Helsinki in Finland wanted to understand what this gene variant could be doing in the pancreas.
Mulder, co-senior author on the study, whose lab studies the pancreas, said:
“Type 2 diabetes is a polygenetic disease, so it’s not one gene that causes the disease: there are probably hundreds of genes that jointly predispose individuals, from which you can infer that the contribution of each individual gene will be quite small."
The study investigated pancreatic islets derived from people who have one or two copies of the risk variant of the MTNR1B gene.
Those who have two copies have higher levels of the melatonin receptor than those with one or no copies. This increase in melatonin receptors makes a person’s pancreas more sensitive to melatonin.
Then the researchers used insulin-secreting cells and mouse islets to increase or decrease the number of melatonin receptors on insulin-producing beta cells. As expected, mice and islets with very few melatonin receptors secreted more insulin in the presence of high levels of melatonin compared to those with many melatonin receptors, from which less insulin was secreted.
This doesn’t mean that the occasional melatonin pill is necessarily dangerous for the one in three people with the MTNR1B risk gene variant or that anyone should rush out and get a genetic test to see if they are carriers.
“This is just a hypothesis, but I think it raises questions that maybe prolonged use of melatonin is not so harmless,” Mulder says.
The researchers will continue to explore the relationship between type 2 diabetes risk genes and the pancreas. They hope their studies will help inform future approaches to personalized medicine.
Tuomi, Nagorny, Singh et al. Increased melatonin signaling is a risk factor for Type 2 Diabetes Cell Metabolism, DOI: 10.1016/j.cmet.2016.04.009
Image: Insulin Molecule. T.Blundell & N Campillo, Wellcome Images