Sex hormone‐binding globulin regulates glucose metabolism in human placental trophoblasts via cAMP/PKA/CREB1

AIM: This study was conducted to investigate the effects of sex hormone‐binding globulin (SHBG) on glucose metabolism and insulin resistance in human placental trophoblasts and involvement of the cAMP/PKA/CREB1 signaling pathway in these effects. METHODS: An insulin resistance cell model of human trophoblasts was established. An SHBG‐overexpression plasmid was transfected into these cells, and the expression of glucose transporter 1 (GLUT1), CREB and p‐CREB was detected and analyzed in normal cells, model cells and all groups of transfected cells by real‐time PCR and western blotting; cAMP, PKA, glucose consumption and pyruvic acid levels were also detected. RESULTS: Among the four groups, there was no significant difference in the expression of CREB mRNA or GLUT1 mRNA (P > 0.05); however, CREB, p‐CREB, GLUT1 protein, cAMP and PKA showed low expression (P < 0.05) and cell glucose consumption and pyruvate production were decreased (P < 0.05) in the model group, compared to the normal group. SHBG overexpression in insulin‐resistant cells partially increased the levels of p‐CREB, GLUT1, cAMP and PKA (P < 0.05). Intracellular glucose consumption and pyruvate production were nearly restored to the levels observed in cells from the normal group. CONCLUSION: Sex hormone‐binding globulin regulates GLUT1 expression via the cAMP/PKA/CREB1 pathway and affects glucose transport in the placenta, which can induce insulin resistance and gestational diabetes.