Non-Coding RNAs as Potential Novel Biomarkers for Early Diagnosis of Hepatic Insulin Resistance

Abstract

In the recent years, the prevalence of metabolic conditions such as type 2 Diabetes (T2D) and metabolic syndrome (MetS) raises. The impairment of liver metabolism resulting in hepatic insulin resistance is a common symptom and a critical step in the development of T2D and MetS. The liver plays a crucial role in maintaining glucose homeostasis. Hepatic insulin resistance can often be identified before other symptoms arrive; therefore, establishing methods for its early diagnosis would allow for the implementation of proper treatment in patients before the disease develops. Non-coding RNAs such as miRNAs (micro-RNA) and lncRNAs (long-non-coding RNA) are being recognized as promising novel biomarkers and therapeutic targets—especially due to their regulatory function. The dysregulation of miRNA and lncRNA activity has been reported in the livers of insulin-resistant patients. Many of those transcripts are involved in the regulation of the hepatic insulin signaling cascade. Furthermore, for several miRNAs (miR-802, miR-499-5p, and miR-122) and lncRNAs (H19 imprinted maternally expressed transcript (H19), maternally expressed gene 3 (MEG3), and metastasis associated lung adenocarcinoma transcript 1 (MALAT1)), circulating levels were altered in patients with prediabetes, T2D, and MetS. In the course of this review, the role of the aforementioned ncRNAs in hepatic insulin signaling cascade, as well as their potential application in diagnostics, is discussed. Overall, circulating ncRNAs are precise indicators of hepatic insulin resistance in the development of metabolic diseases and could be applied as early diagnostic and/or therapeutic tools in conditions associated with insulin resistance.