title: Role of miRNAs in the pathogenesis and susceptibility of diabetes mellitus.
abstract: MicroRNAs (miRNAs) are noncoding RNAs of ~22 nucleotides that regulate gene expression post-transcriptionally by binding to the 3' untranslated region of messenger RNA (mRNAs), resulting in inhibition of translation or mRNA degradation. miRNAs have a key role in fine-tuning cellular functions such as proliferation, differentiation and apoptosis, and they are involved in carcinogenesis, glucose homeostasis, inflammation and other biological processes. In this review, we focus on the role of miRNAs in the pathophysiology of the metabolic disease and diabetes mellitus, the hallmark of which is hyperglycemia caused by defective insulin secretion and/or action. A growing number of studies have revealed the association between miRNAs and the processes of insulin production and secretion in pancreatic β cells. In addition, aberrant expression of miRNAs in skeletal muscle, adipose tissue and liver has also been reported. Intriguingly, the tumor suppressor p53 has been implicated in the pathogenesis of diabetes in association with a number of miRNAs, suggesting that a p53/miRNA pathway might be a therapeutic target. Moreover, data from genome-wide association studies have revealed that several miRNA target sequences overlap type 2 diabetes susceptibility loci. Finally, the recent discovery of circulating miRNAs associated with diabetes onset/progression suggests the potential use of miRNAs as biomarkers.
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Division of Diabetes, Endocrinology and Metabolism, Chiba University Hospital, Chiba, Japan.|AMED-CREST, AMED, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Chiba University Hospital, Chiba, Japan.|AMED-CREST, AMED, Japan Agency for Medical Research and Development, Tokyo, Japan.|Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D015415:Biomarkers / Q000097:blood; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D035683:MicroRNAs; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53