MicroRNAs in β-Cell Biology, Insulin Resistance, Diabetes and Its Complications

Abstract

MicroRNAs (miRNAs) are small 19–23 nucleotide RNA molecules that act as regulators of protein expression in eukaryotic cells by inducing the translational arrest and degradation of messenger RNAs (1). They are potent drivers of differentiation and development (1), and their dysregulation has been linked to many diseases. Here, we present an overview of the known and proposed roles and effects of miRNAs in type 1 and type 2 diabetes (T1D and T2D), focusing on β-cell biology, insulin resistance, and diabetes complications. Specifically, we discuss miRNAs in β-cell biology, altered expression of miRNAs in adipose tissue in response to obesity, and miRNA dysfunction in organs and tissues that may be affected in later stages of the disease. Additionally, we propose a set of research directions that may yield novel diagnostic and therapeutic approaches for this chronic illness. T2D is characterized by hyperglycemia resultant from impaired insulin secretion and/or impaired insulin action in peripheral tissues (2). T2D constitutes one of the greatest pandemics of our time, with 220 million people currently diagnosed (3), and 366 million people expected to be affected by 2030 (4). A number of lines of evidence support a key role for pancreatic β-cell dysfunction in T2D (in addition to T1D), in which it is the major pathology. For example, recent genome-wide association studies have strongly implicated genes involved in insulin secretion as etiological factors in the development of T2D (5). A role for miRNAs in T2D was first established in 2004 by Poy et al. (6) who showed that miR-375 is directly involved in the regulation of insulin secretion. This study was one of the first to demonstrate that a miRNA could be tightly linked to a disease phenotype. In recent years, dozens of additional miRNAs have been identified as components of pathways triggered by, or contributing …