Adiponectin Promotes SHBG Expression in Trophoblast Cells and Improves Insulin Signaling in Streptozotocin-Induced Gestational Diabetes Mellitus Rats

Objective This study aimed to explore the possible mechanism of Adiponectin on the Insulin signaling in streptozotocin (STZ)-induced gestational diabetes mellitus (GDM) rats. Methods The GDM rats were induced by injection of 40 mg/kg STZ, and then orally treated with Adiponectin (5, 10, 20 mg/kg) every day from gestation day (GD)7 to GD20. The body weight and fasting blood glucose (FBG) were observed every 3 days from GD9 to GD18. Meanwhile, the Insulin tolerance test (ITT), homeostasis model assessment Insulin resistance (HOMA-IR), and Adiponectin expression were observed in rats. Moreover, the Insulin signaling-related factors, sex hormone-binding globulin (SHBG), PPAR-α, phospho-AMPK alpha, glucose transporter-3 (GLUT3), and phospho-insulin receptor substrate-1 (p-IRS1) in placental tissues were measured in rats. In vitro, HTR-8-Svneo cells were induced by 30 mM glucose and then treated with Adiponectin (50, 100, 200 ng/mL) to observe the changes in cell viability, SHBG expression, and the Insulin signaling-related factors. Moreover, silencing or overexpression of SHBG was achieved via transfection with siRNA or pEX-4 SHBG, respectively. The effects of SHBG on the Insulin signaling-related factors were observed in cells. Results Adiponectin treatment significantly improved the STZ-induced decrease in body weight, increase in the FBG, ITT, and HOMA-IR with increasing doses. Specifically, Adiponectin treatment upregulated the SHBG expression and the Insulin signaling-related factors (PPAR-α, p-AMPK, GLUT3, and p-IRS1) in the placental tissues of GDM rats with increasing doses. In line with the results of animal experiments, Adiponectin treatment alleviated the high glucose-induced decrease in cell viability, SHBG expression, and the levels of GLUT3 and p-IRS1 in HTR-8-Svneo cells with increasing doses. Moreover, the levels of GLUT3 and p-IRS1 were regulated by the SHBG expression. SHBG silencing weakened the effect of Adiponectin in improving the levels of GLUT3 and p-IRS in the high-glucose-induced cells. Conclusion The study showed that Adiponectin upregulated the SHBG expression and improved the Insulin signaling in STZ-induced GDM rats, as well as Adiponectin upregulated the Insulin signaling-related factors via SHBG in high-glucose-induced trophoblast cells. This study suggests that Adiponectin may be a potential therapeutic target in GDM.

Adiponectin; Gestational diabetes mellitus; HTR-8-Svneo cell; Sex hormone-binding globulin; Streptozotocin.