Long Noncoding RNAs in the Pathogenesis of Insulin Resistance

Figures

• 

  Figure 1. A deregulated lncRNA profile is involved in the pathogenesis of insulin resistance and dysregulated glycolipid metabolism in various tissues. Under the condition of metabolic disorders, the declined expression of lncRNAs are marked in blue, and the increased expression of lncRNAs are marked in red, while those with unknown or controversial expression are marked in black in liver, skeletal and adipose tissues. Generally, upregulated lncRNAs are negative regulators of the insulin signaling pathway, while downregulated lncRNAs exert beneficial effects on insulin sensitivity and glycolipid metabolism. INSR, insulin receptor; IRSs, insulin receptor substrates.

• 

  Figure 2. LncRNAs are important regulators of the insulin signaling pathway and glycolipid metabolism in the liver. LncRNAs including GAS5, lncARSR and lncSHGL positively regulate the PI3K/Akt pathway, while lncRNAs including EPIB41L4A-AS1 and NONMMUT031874.2 negatively regulate the PI3K/Akt pathway in the liver. Other lncRNAs interact with downstream molecules of the PI3K/Akt pathway to regulate glucose and lipid metabolism: H19 activates mTOR complex, MEG3 stimulates FOXO1 and its downstream gluconeogenic enzymes, Blnc1 activates the LXR/SREBP-1c pathway, and MALAT1 upregulates the expression of SREBP-1c to promote hepatic gluconeogenesis and lipid deposition. Akt, protein kinase B; FAS, fatty acid synthase; FOXO1, forkhead box o1; G6Pase, glucose-6-phosphatase; INSR, insulin receptor; IRSs, insulin receptor substrates; LXR, liver x receptor; mTOR, mammalian target of rapamycin; PEPCK, phosphoenolpyruvate carboxykinase; PI3K, phosphatidylinositol 3-kinase; PIP3, phosphatidylinositol (3,4,5)-triphosphate; S6K, ribosomal protein S6 kinase; SREBP-1c, sterol regulatory element binding protein-1c.