| Literature DB >> 24374217 |
Vasumathi Kameswaran1, Nuria C Bramswig1, Lindsay B McKenna1, Melinda Penn1, Jonathan Schug1, Nicholas J Hand2, Ying Chen3, Inchan Choi1, Anastassios Vourekas4, Kyoung-Jae Won1, Chengyang Liu5, Kumar Vivek5, Ali Naji6, Joshua R Friedman2, Klaus H Kaestner7.
Abstract
Type 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing β cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RNAs of human islets from diabetic and nondiabetic organ donors. We identified a cluster of microRNAs in an imprinted locus on human chromosome 14q32 that is highly and specifically expressed in human β cells and dramatically downregulated in islets from T2DM organ donors. The downregulation of this locus strongly correlates with hypermethylation of its promoter. Using HITS-CLIP for the essential RISC-component Argonaute, we identified disease-relevant targets of the chromosome 14q32 microRNAs, such as IAPP and TP53INP1, that cause increased β cell apoptosis upon overexpression in human islets. Our results support a role for microRNAs and their epigenetic control by DNA methylation in the pathogenesis of T2DM.Entities:
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Year: 2013 PMID： 24374217 PMCID： PMC3932527 DOI： 10.1016/j.cmet.2013.11.016
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287