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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.

 Read more at Lund University’s press release...




September 2009
ENGAGE Young Investigator


Valeriya Lyssenko MD, PhD Department of Clinical Sciences, Diabetes and Endocrinology, Lund University
CRC, University Hospital Malmö, 20502 Malmö, Sweden

Interests and role in ENGAGE   Valeriya’s main research interest is to describe genetic and clinical risk factors associated with increased risk of type 2 diabetes. One of her key projects evaluates the role of genetic variants in the prediction of type 2 diabetes using prospective cohorts. Together with the Broad Institute (MIT/Harvard), Novartis and Lund University, she also worked on a Diabetes Genetic Initiative (DGI), a whole genome association study (GWAS) for type 2 diabetes (500,000 SNPs). In 2008 she received Young Investigator Award from the Scandinavian Society for the Study of Diabetes, and in 2009 a Rising Star Award from the European Association for the study of Diabetes. Within ENGAGE Valeriya is involved in work within WP 7- Clinical Translation. Currently, she is also coordinating efforts of ENGAGE cohorts to study the association between variants in the MTNR1B gene with sleep disorders and risk of type 2 diabetes.