Effect Of SelS Gene Silence On Glucosamine-induced Insulin Resistance

Diabetes has a serious impact on human health, so that the study of diabetesprevention has become a hot topic. A large number of studies have shown that insulinresistance is a major risk factor for type2diabetes. Hexosamine biosynthesis pathway(HBP) is a branch of glucose metabolic pathways and plays an important role for insulinresistance in the occurrence and development of diabetes. What is more, HBP andendoplasmic reticulum stress is closely related to insulin resistance and diabetes.Selenoprotein S (SelS) is an endoplasmic reticulum (ER) and plasma membraneresident protein. Previous studies reveal that SelS protects cells from oxidative damage andis considered an important component of retro-translocation channel in endoplasmicreticulum associated protein degradation. SelS suppresses endoplasmic reticulumstress-induced apoptosis and participates in the inflammatory response.In this article, gene silence, real-time quantitative PCR, western blotting and so onwere used to study the effect of SelS gene silence on the insulin signal transductionmolecules expression and phosphorylation. The results showed that glucosamine-inducedendoplasmic reticulum stress in HepG2cells led to the increase of SelS, GRP78andGSK-3β protein expression and decrease of Akt and p-GSK-3β protein level. When SelSwas treated with gene silence, glucosamine further increased protein expression of GRP78,further decreased insulin-stimulated p-GSK-3β protein level. Moreover, gene silence ofSelS also led to the decrease of insulin-stimulated p-Akt protein level. These results suggestthat SelS gene silence exacerbates glucosamine-induced endoplasmic reticulum stress, andinfluences the expression and phosphorylation of insulin signal transduction molecules,suggesting that SelS plays an importance role in insulin resistance.