Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.

ABSTRACT: Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. 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 also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets. Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose w

SUBMITTER: Lyssenko V 

PROVIDER: S-EPMC3725650 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature