Abstract
Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.
Highlights
Insulin resistance (IR) is a clinical condition defined as a reduced metabolic response to the action of insulin on target tissues, which are unable to coordinate a normal glucoselowering response involving the suppression of endogenous glucose production, the suppression of lipolysis, cellular uptake of available plasma glucose, and glycogen synthesis
They identified that, in the absence of H19, p53 significantly occupied the forkhead box O1 (FoxO1) promoter, suggesting that the inhibition of H19 promotes the transcription of FoxO1 through p53. They demonstrated that the inhibition of H19 in vivo induced hyperglycemia and hyperinsulinemia and increased the transcription of hepatic gluconeogenic genes. These results suggest that H19 inhibition deregulates both circulatory and metabolic profiles and hepatic gluconeogenesis, possibly via the p53/FoxO1 axis (Figure 2) [58]
Of miR-214 to upregulate activating transcription factor 4 (ATF4) expression, leading to the activation of FoxO1 and fatty acid synthase (FAS), which in turn promotes lipogenesis and insulin resistance (IR) [76]. These researchers proposed that cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) induces maternally expressed gene 3 (MEG3) upregulation and increases the hepatic gluconeogenic genes PGC-1α, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase catalytic (G6PC) through the CREB–CREB-regulated transcriptional coactivator (CRTC2) complex, which contributes to the pathogenesis of hepatic gluconeogenesis, suggesting that MEG3 acts as a Competing endogenous RNAs (ceRNA) to upregulate CRTC2 via miR-302a-3p (Figure 3) [77]
Summary
Insulin resistance (IR) is a clinical condition defined as a reduced metabolic response to the action of insulin on target tissues, which are unable to coordinate a normal glucoselowering response involving the suppression of endogenous glucose production, the suppression of lipolysis, cellular uptake of available plasma glucose, and glycogen synthesis. An essential factor that contributes to IR is the decreased phosphorylation of tyrosine residues (Tyr) in the β-subfraction of IR, which results in a decrease in its interaction with phosphatidylinositol 3-kinase (PI3K) and alters the phosphorylation and activation of protein kinase B (AKT) [3]. Several factors, such as proinflammatory cytokines, saturated fatty acids (SFAs), amino acids, endothelin 1, angiotensin II, and hyperinsulinemia, increase kinase activity [2,4]. The aim of this review was to analyze the function and molecular mechanisms of the main lncRNAs involved in IR development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
