Influence of miRNA in insulin signaling pathway and insulin resistance: micro-molecules with a major role in type-2 diabetes

Abstract

The prevalence of type-2 diabetes (T2D) is increasing significantly throughout the globe since the last decade. This heterogeneous and multifactorial disease, also known as insulin resistance, is caused by the disruption of the insulin signaling pathway. In this review, we discuss the existence of various miRNAs involved in regulating the main protein cascades in the insulin signaling pathway that affect insulin resistance. The influence of miRNAs (miR-7, miR-124a, miR-9, miR-96, miR-15a/b, miR-34a, miR-195, miR-376, miR-103, miR-107, and miR-146) in insulin secretion and beta (β) cell development has been well discussed. Here, we highlight the role of miRNAs in different significant protein cascades within the insulin signaling pathway such as miR-320, miR-383, miR-181b with IGF-1, and its receptor (IGF1R); miR-128a, miR-96, miR-126 with insulin receptor substrate (IRS) proteins; miR-29, miR-384-5p, miR-1 with phosphatidylinositol 3-kinase (PI3K); miR-143, miR-145, miR-29, miR-383, miR-33a/b miR-21 with AKT/protein kinase B (PKB) and miR-133a/b, miR-223, miR-143 with glucose transporter 4 (GLUT4). Insulin resistance, obesity, and hyperlipidemia (high lipid levels in the blood) have a strong connection with T2D and several miRNAs influence these clinical outcomes such as miR-143, miR-103, and miR-107, miR-29a, and miR-27b. We also corroborate from previous evidence how these interactions are related to insulin resistance and T2D. The insights highlighted in this review will provide a better understanding on the impact of miRNA in the insulin signaling pathway and insulin resistance-associated diagnostics and therapeutics for T2D.