Microwave-assisted synthesis of chitooligosaccharide guanidine and its effect on GLUT4-dependent glucose uptake through an Akt-activated protein kinase signaling pathway in L6 skeletal muscle cells

Abstract

With reference to the molecular structure of metformin, a new biguanide compound, namely, chitooligosaccharide guanidine (COSG), was synthesized by microwave irradiation. It could both reduce the stimulatory effect of metformin on the gastrointestinal system and increase the biological activity of the drugs. Then, a cell vitality test was conducted to examine the cell toxicity of chitooligosaccharide (COS) and COSG, and an insulin resistance (IR) model using L6 skeletal muscle cells was established. The influence of COS and COSG on the cell vitality and glucose consumption of IR cells was observed and compared with that of metformin and insulin. Moreover, the expression and translocation of GLUT4 protein and the phosphorylation level of Akt were further investigated to study the mechanism. The results showed that both COS and COSG were non-toxic and could improve the vitality and promote the uptake of glucose of L6 cells remarkably in comparison to metformin. Furthermore, the effect of COSG on promoting glucose uptake was better and dose-dependent. It was also found that COS could increase the total expression of GLUT4 protein but had no significant effect on the membrane translocation of GLUT4, whereas metformin exhibited little effect on either the total expression or the membrane expression of GLUT4. Moreover, COSG exerted little influence on the total expression of GLUT4 protein but led to significant improvement in the membrane expression of GLUT4 and phosphorylation level of Akt, which were consistent with the effect of insulin.