Riboregulators and Metabolic Disorders: Getting Closer Towards Understanding the Pathogenesis of Diabetes Mellitus?

Abstract

Type 2 Diabetes occurs as a result of defects in insulin secretion and its function. Although mechanisms of disease are not fully elucidated, it is recognized that a progressive decline in insulin secretory capacity is responsible for its occurrence and natural course. Metabolic syndrome, known to be a precursor of Type 2 diabetes, is characterized by a constellation of vascular risk factors, with obesity playing a central role. Obesity contributes to impaired insulin function and abnormal glucose metabolism. MicroRNAs (miRNA) are highly conserved, small, RNA molecules encoded in the genomes of plants and animals and they regulate the expression of many other genes either by RNA interference (RNAi) or RNA activation (RNAa). miRNAs have been found to regulate multiple genes and seem to be crucial factors in many cellular pathways, including development, cell differentiation, proliferation and apoptosis. Pancreatic islet cell specific miRNAs which regulate insulin secretion, and adipocyte specific miRNAs which regulate adipocyte differentiation, are examples of miRNAs that are predicted to have crucial roles in governing glucose homeostasis. Further understanding of the roles of miRNAs in glucose metabolism may unravel better understanding of pancreatic cell biology and diabetes pathophysiology, allowing for newer therapeutic targets and strategies. In this review, we will be discussing about the role/function of miRNAs in insulin secretion and regulation, lipid metabolism and conditions like hypertension and cardiovascular diseases and the potential use of miRNA in therapy.

MicroRNA 144 Impairs Insulin Signaling by Inhibiting the Expression of Insulin Receptor Substrate 1 in Type 2 Diabetes Mellitus

“…Among more than 10000 miRNAs identified in 115 species so far [Sanger miRNA database release 14.0 http://www.mirbase.org/], only a handful have been linked to glucose metabolism and metabolic disorders [30]. Among them, miR-375 that is abundantly expressed in pancreatic and beta cells, negatively regulates glucose-stimulated insulin secretion via myotrophin ( Mtpn ) inhibition [31], [32].…”

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

“…Binding to regulatory sites of target mRNA, miRNAs modify their expression by translational repression or target mRNA degradation to cause decreased protein production [25]. MiRNAs are involved in the regulation of insulin secretion and response and in glucose homeostasis [26]. Moreover, they are required in adipocyte differentiation and fatty acid synthesis in hepatocytes [27].…”

Circulating miRNAs as Predictive Biomarkers of Type 2 Diabetes Mellitus Development in Coronary Heart Disease Patients from the CORDIOPREV Study

“…In the latter case, it has been demonstrated that extracellular vesicles circulating in human plasma, which are a mixture of microparticles, exosomes, and other structures such as apoptotic bodies, contain miRNAs that can be considered as a novel class of signaling molecules mediating intercellular communication. 14 Some of these circulating miRNAs have been linked to glucose metabolism, 15 while others, such as miR-144 , miR-146a , miR-150 , miR-182 , miR-192 , mir-29a , miR-30d , and miR-320 , seem to participate in the regulation of insulin signaling. 16 , 17 There are others, too, such as miR-375 , 18 , 19 , 20 , 21 miR-96 , 22 and miR-124a , 23 which have been associated with the development of T2DM and may also be involved in its progression.…”