Variants in a gene encoding a receptor for melatonin that increase the risk of type 2 diabetes, are reported in three studies published online in Nature Genetics. They provide the first genetic evidence in humans for a link between melatonin, which regulates the body clock, and type 2 diabetes.
Melatonin is known to regulate the roughly 24-hour cycle of living things -- their circadian rhythm -- and insulin levels vary within this cycle, with them being at their lowest point at night. Some previous evidence linked disturbances of circadian rhythmicity to diabetes, and these studies provide a hereditary link.
In order to try and identify variants associated with differences in levels of blood glucose, which constitutes a risk factor for type 2 diabetes, data from several previous genome-wide association studies were pooled. Goncalo Abecasis and colleagues report that a variant in MTNR1B, encoding one of the two human melatonin receptors, increases risk of both blood glucose levels and type 2 diabetes.
Philippe Froguel and colleagues report a similar result for a nearby variant which neighbours MTNR1B. A third team, led by Leif Groop, confirms this genetic result. They also report that individuals with the MTNR1B risk variant have increased expression of MTNR1B in the insulin-producing cells of the pancreas, and that melatonin inhibits insulin release from pancreatic beta cells in response to glucose.
All three studies suggest that inherited variation in at least one of the melatonin receptors may predispose to diabetes via direct effects of melatonin on insulin secretion.
Goncalo Abecasis (University of Michigan, Ann Arbor, MI, USA)
Leif Groop (Lund University, Malmo, Sweden)
Philippe Froguel (Imperial College London, UK)
Abstracts available online:
Paper 1 Abstract.
Paper 2 Abstract.
Paper 3 Abstract.
(C) Nature Genetics.
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