Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

Purpose: Extracellular vesicles (EVs) were obtained from ocular samples and plasma of diabetic retinopathy (DR) patients who were having cataract and/or vitrectomy surgeries. Methods: Aqueous, vitreous, and plasma were collected from six patients with proliferative DR (PDR), also aqueous and plasma were collected from seven patients with non-PDR (NPDR), and seven patients with cataract (control group). EVs were isolated using the membrane affinity column method. Nanoparticle tracking analysis technique was used to measure the size and concentration of particles. Results: The mean size of EVs in aqueous was smaller in the PDR group comparing with the other two groups (P < 0.05). Besides, EVs concentration in plasma was higher in the PDR group than in the NPDR group (P < 0.05). Conclusion: We successfully isolated and measured EVs in ocular samples and plasma from DR patients. Further studies must be conducted to identify protein and molecular contents to better understand the role of particles in the pathophysiology of DR and their potential as a biomarker or medicinal target.