Melatonin signalling may contribute to Type 2 diabetes
medwireNews: Researchers have discovered how a common variant of the melatonin receptor 1b gene (MTNR1B) burdens carriers with an increased risk of developing Type 2 diabetes.
As reported in Cell Metabolism, Hindrik Mulder (Lund University Diabetes Centre, Sweden) and colleagues found that each copy of the risk allele resulted in a doubling of MTNR1B expression in human islet cells, enhancing the suppression of insulin release by melatonin.
And they show that 23 nondiabetic people with two copies of the risk allele had lower melatonin levels than 22 with no risk alleles, along with higher glucose levels and a lower corrected insulin response during an oral glucose tolerance test (OGTT). Three months of taking melatonin 4 mg at bedtime increased glucose levels and reduced insulin response in all participants, but more so in the risk allele carriers, and most particularly for insulin response during the first 30 minutes of the OGTT.
Experiments in mice indicated that the effects of reduced melatonin signalling on insulin release were mediated via cAMP, leading the researchers to speculate that people with the MTNR1B risk variant may have reduced cAMP levels in their pancreatic β cells.
“In view of this, incretin-based therapy, which amplifies cAMP signaling in β cells, may be particularly well suited for these patients”, they say.
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