Implications of microRNAs in the pathogenesis of diabetes
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REVIEW
Implications of microRNAs in the pathogenesis of diabetes Seung-Yoon Park • Hyo-Jin Jeong Won-Mo Yang • Wan Lee
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Received: 7 October 2012 / Accepted: 24 December 2012 / Published online: 30 January 2013 Ó The Pharmaceutical Society of Korea 2013
Abstract Diabetes is a complex metabolic disease with an etiology that includes genetic, epigenetic and environmental factors that lead to several different defects of glucose homeostasis, primarily in the pancreatic b-cells, liver, muscle, and adipose tissues. MicroRNAs (miRNAs) have recently emerged as important regulators in posttranscriptional gene expression. Although the target genes and biological functions of individual miRNAs remain largely unknown, previous studies have shown them to be important regulators of diverse biological processes, in both normal and pathological states. In the past decade, an increasing number of studies have focused on the regulatory roles of miRNAs in metabolism; thus, miRNAs play an important role in the pathogenesis of diabetes. This review summarizes recent findings related to the roles of miRNAs in diabetes. The information presented herein might be useful for the future development of miRNAs as diagnostic and therapeutic targets in diabetes. Keywords MicroRNA Diabetes Insulin resistance Metabolic disease
Introduction Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by impaired glucose homeostasis that results in hyperglycemia due to increased insulin resistance in insulin sensitive tissues (liver, skeletal muscle, adipose tissue, etc.) and/or disturbance in insulin S.-Y. Park H.-J. Jeong W.-M. Yang W. Lee (&) Department of Biochemistry, Dongguk University School of Medicine, 87 Dongdae-ro, Gyeongju 780-714, Korea e-mail: [email protected]
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secretion in pancreatic b-cells (Kahn et al. 2006; Petersen and Shulman 2006; Samuel and Shulman 2012). The prevalence of diabetes is rapidly growing worldwide, and it is currently the most common metabolic disorder. Specifically, diabetes affected 285 million adults in 2010, and this is expected to increase to 7.7 % or 439 million adults by 2030 (Shaw et al. 2010). Although type 2 DM (T2DM), which is characterized by insulin resistance, is the most prevalent form, both type 1 and 2 diabetes cause vascular complications, such as nephropathy, retinopathy, and microangiopathy, which increase the risk of death due to ischemic heart disease, renal failure, and stroke (Bornfeldt and Tabas 2011). The etiology of diabetes is not completely understood, but it is mainly attributable to genetic factors, lifestyle, obesity, and high calorie diet (Shaw et al. 2010). MicroRNAs (miRNAs) are short single-stranded RNA molecules and one of the largest gene families, comprising *1 % of the genome (Bartel 2009). In 1993, miRNAs were first reported in C. elegans as RNA molecules that were found to regulate the developmental timing in the organism (Lee et al. 1993); however, after less than two decades, thousands of miRNAs have been identified in plants and
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