Diabetes mellitus, a microRNA-related disease?

Abstract

Diabetes mellitus is a complex disease resulting in altered glucose homeostasis. In both type 1 and type 2 diabetes mellitus, pancreatic β cells cannot secrete appropriate amounts of insulin to regulate blood glucose level. Moreover, in type 2 diabetes mellitus, altered insulin secretion is combined with a resistance of insulin-target tissues, mainly liver, adipose tissue, and skeletal muscle. Both environmental and genetic factors are known to contribute to the development of the disease. Growing evidence indicates that microRNAs (miRNAs), a class of small noncoding RNA molecules, are involved in the pathogenesis of diabetes. miRNAs function as translational repressors and are emerging as important regulators of key biological processes. Here, we review recent studies reporting changes in miRNA expression in tissues isolated from different diabetic animal models. We also describe the role of several miRNAs in pancreatic β cells and insulin-target tissues. Finally, we discuss the possible use of miRNAs as blood biomarkers to prevent diabetes development and as tools for gene-based therapy to treat both type 1 and type 2 diabetes mellitus.

Application of microRNAs in diabetes mellitus

“…Upregulation and downregulation of miRNAs are strongly associated with T1D and T2D. miRNAs directly target genes involved in b-cell survival and insulin exocytosis, and insulin resistance is the central mechanism of miRNAs-mediated T1D and T2D (FernandezValverde et al 2011, Guay et al 2011, Rottiers & Naar 2012, Samuel & Shulman 2012, Williams & Mitchell 2012. Manipulation of miRNAs and insulin signaling may have therapeutic potential.…”

Role of islet microRNAs in diabetes: which model for which question?

“…Overall, these and many other studies (reviewed extensively elsewhere [1][2][3]) have identified microRNAs as essential players in beta cell development and function and in the regulation of whole body glucose homeostasis.…”

“…A growing number of studies demonstrate that these changes are not only caused by deregulation of key transcription factors such as v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian) (MafA) or pancreatic and duodenal homeobox 1 (PDX1) but are also driven by modifications in the level of another group of molecules regulating gene expression, the microRNAs [1][2][3][4]. MicroRNAs are small non-coding RNAs (typically 21-23 nucleotides long) that pair to the 3′ untranslated region of target mRNAs leading to translational repression and/or a decrease in messenger stability [5].…”

Genetic and Epigenetic Factors in Etiology of Diabetes Mellitus Type 1

“…Prolonged exposure to cytokines leads to a decreased capacity of b cells to produce and release insulin in response to secretagogues and, in the long term, destruction of the cells by apoptosis or necrosis. 25,28 T1D typically affects young children, with onset as early as 1 year of age; most cases are diagnosed before the patient is 18 years old. The autoimmune process starts even earlier, as evidenced by the presence of autoantibodies in serum against T1D-specific antigens.…”

“…87 In light of these results, measurement of specific miRNA levels may be useful for identifying people at risk for developing T1D, possibly preventing the development of the disease. 28 Lentiviral transgenesis has been used to generate NOD mice in which the Slc11a1 T1D candidate gene was silenced by RNA interference. Silencing reduced the frequency of T1D, thus demonstrating a role for Slc11a1 in modifying susceptibility to T1D.…”