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Sex hormone‐binding globulin regulates glucose metabolism in human placental trophoblasts via cAMP/PKA/CREB1
Author(s) -
Chi Xinshu,
Feng Chong,
Wang Xiaoyan,
Jin Zhen
Publication year - 2020
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.14429
Subject(s) - glut1 , creb , medicine , endocrinology , glucose transporter , creb1 , insulin resistance , sex hormone binding globulin , carbohydrate metabolism , placenta , insulin , biology , hormone , fetus , biochemistry , transcription factor , gene , pregnancy , genetics , androgen
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.