Upregulation of Klotho Aggravates Insulin Resistance in Gestational Diabetes Mellitus Trophoblast Cells

Abstract

Klotho expression was up-regulated in HG-induced cells. Overexpression of klotho could reduce the cell viability, insulin signaling molecules (INSR-<i>α</i>, INSR-<i>β</i>, IRS1, IRS2, and GLUT4), and glucose uptake in HTR-8/SVneo cells of the HG group. In addition, the overexpression of klotho inhibited the levels of IGF-1, IGF-1R/p-IGF-1R, and the phosphorylation and activation of the signal transduction molecules PI3K/Akt/mTOR. On the contrary, klotho deletions could reverse these changes of HTR-8/SVneo cells induced by HG<i>. Conclusion</i>. In a word, the results of this study showed that the regulation of klotho played an important role in the IR of trophoblast cells induced by HG, which was mediated at least in part by the IGF-1/PI3K/Akt/mTOR pathway.