MTNR1B associates with increased risk of future T2D and impaired early insulin secretion

Genome-wide association studies have significantly contributed to rapid progress in genetics of type 2 diabetes (T2D). However, it is still a challenge to understand the underlying biology for many of genetic variants. One way to get more insights into pathophysiology of disease is to explore association between genetic markers and disease-related phenotypes. Recently, an intriguing link was observed that a common variant in the gene encoding the melatonin recreptor 1B (MTNR1B) was associated with impaired insulin secretion, elevated glucose concentrations and increased risk of future T2D. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We could show that the MTNR1B mRNA is expressed in human islets, and non-diabetic individuals carrying the risk allele and patients with T2D showed increased expression of the receptor in islets. Insulin release from clonal β-cells in response to glucose was inhibited in the presence of melatonin. Inhibition of melatonin effects in islets could thus represent a novel therapeutic target. Melatonin - is a circulating hormone, primarily released from the pineal gland, and known as a regulator of seasonal and circadian rhythms. There is also a well-established link between sleep disorders and T2D. Preliminary data suggest that variants in the MTNR1B gene partially explains this association.

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