Melatonin and Type 2 Diabetes Risk

A study published in Cell Metabolism suggests that the MTNR1B receptor makes cells more sensitive to melatonin and is a risk factor for type 2 diabetes.

MTNR1B is a slightly altered melatonin receptor gene that is 1 out of more than 100 known risk factors for type 2 diabetes. Up to 30% of the population may be predisposed to having a pancreas that is more sensitive to melatonin and its insulin-inhibiting effects.

“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,” said study co-senior author Hindrik Mulder.

Data from pancreatic islets derived from humans with 1 or 2 copies of the risk variant of MTNR1B was presented. Individuals with 2 copies were found to have higher levels of the melatonin receptor compared with individuals with 1 or 0 copies. The increase in melatonin receptors causes the pancreas to become more sensitive to melatonin.

Next, researchers used insulin-secreting cells and mouse islets and increased or decreased the amount of melatonin receptors on insulin-producing beta cells. The mice and islets with fewer melatonin receptors secreted more insulin when in the presence of high levels of melatonin compared with a high number of receptors, where less insulin was secreted.

To test their hypothesis, researchers used 23 non-diabetic people with the MTNR1B risk gene variant and 22 without. Each individual was required to take 4 milligrams of melatonin at bedtime for 3 months. The results of the study revealed that participants without the risk gene variant had 3 times the level of insulin secretion compared with participants who had the gene variant.

“We don't typically eat or are physically active at night, so our energy demands drop and we don't need maximum insulin secretion,” Mulder said. “A likely explanation is that, as melatonin levels rise, they tell our beta cells not to release as much insulin.”

Although these results spark questions, researchers state that it does not necessarily mean patients with the MTNR1B risk gene variant who take a melatonin pill occasionally are in danger.

“This is just a hypothesis, but I think it raises questions that maybe prolonged use of melatonin is not so harmless,” Mulder said.

Further research will be conducted as researchers examine the relationship between the type 2 diabetes risk genes and the pancreas.