Downregulated ABHD5 Aggravates Insulin Resistance of Trophoblast Cells During Gestational Diabetes Mellitus.

Abstract

Lipid metabolism-associated molecule abhydrolase domain containing 5 (ABHD5) has been reported to have a role in insulin-mediated glucose uptake, the deregulation of it is associated with gestational diabetes mellitus (GDM). However, whether ABHD5 participates in glucose metabolism disorders in GDM patients has remained elusive. The present study aimed to clarify the role of ABHD5 in regulating insulin signaling in placentae during GDM. Reverse transcription-quantitative polymerase chain reaction (qRT-PCR) analysis was used for detecting the levels of ABHD5 and AMP kinase (AMPK), the insulin signaling molecules insulin receptor (INSR), INSR substrate (IRS1, IRS2), phosphoinositide 3-kinase (PI3K) and AKT, as well as the glucose transporter type 4 (GLUT-4) in placentae and the trophoblast cell line HTR-8/SVneo, while the protein level of ABHD5 was determined by western blotting. Pearson correlation analysis was performed to assess the correlation between the levels of ABHD5 and AMPK in placentae. In addition, ABHD5 overexpression in HTR-8/SVneo cells was achieved using plasmid vectors. The results indicated that the expression of ABHD5 and AMPK was dampened in placental tissues of females with GDM, and the levels of ABHD5 were positively correlated with AMPK. High-glucose (HG) treatment suppressed the expression of ABHD5, AMPK, GLUT-4, INSR, IRS, PI3K, and AKT in HTR-8/SVneo cells, and the overexpression of ABHD5 caused an elevation of the expression of these genes under normal and HG conditions in vitro. In conclusion, HG conditions induce insulin resistance of HTR-8/SVneo cells through downregulating ABHD5, which may account for impaired insulin signaling of placental tissues in GDM women.