[The impacts of testosterone on insulin sensitivity and chronic low-grade].

Objectives: Insulin resistance (IR) is a common manifestation in patients with polycystic ovarian syndrome (PCOS). Both clinical observations and animal studies have demonstrated that IR could be induced by hyperandrogenemia, which is the charac-teristic of PCOS.Nevertheless, the mechanisms of IR in PCOS are still unclear especially at the molecular level.We conduct this study to ellucidate the effects of androgen on insulin sensitivity and chronic low-grade inflammation in adult C57BL/6 female mice. Methods: Eleven adult female C57BL/6 mice aged 8 weeks weredaily injected with testosterone (1.0 mg/100 g body weight)which dissolved in sesame oil (experimental group T) for 16 weeks.Ten control mice were injected with sesame oil only (group Con). The changes of body weight and body fat content were detected.Intraperitoneal glucose tolerance tests (IGTT) were performed at 0, 2, 3 and 16 weeks treatment, blood from tail vein was taken to detect levels of glucose.Intraperitoneal insulin tolerance tests (ITT) were performed at 16 weeks treatment.Both groups were sacrificed after16 weeks treatment, and phosphorylation of GSK3βand InsR, two molecules of insulin signaling pathway, were detected by Western blot from adipose tissue.The phosphorylation of NF-κBp65, CD16/32, and CD206 were also detected in adipose tissues.ELISA was used totest the serum IL-6 and MCP-1. Results: (1) No obvious significance of body weight as well as body fat content was detected between both experimental groups ( P >0.05); (2) 2 weeks treatment with testosterone induced the in-crease of fasting blood glucose and displayed obvious significance compared with group Con ( P <0.05); (3) 3 weeks treatment with testosterone induced the increase of area under the curve (AUC) of the blood glucose following IGTT and displayed significance compared with group Con ( P <0.05). And more obvious significance was detected at 16 weeks treat-ment ( P <0.01); (4) 16 weeks treatment with testosterone induced the increase of AUC of the blood glucose following ITT( P <0.01); (5) the serum IL-6 and MCP-1 in testosterone treat-ment was higher than that in thecontrols ( P <0.05). And 16 weeks treatment with testosterone decreased phosphorylation of GSK3β and InsR in C57BL/6 adipose tissues ( P <0.05), in-creased phosphorylation of NF-κBp65.Testosteroneenhanced the expression of CD206, and decreased the expression of CD16/32. Conclusions: Treatment with testosterone in adult fe-male mice can induce insulin resistance by blocking insulin signal transduction, without in-fluencing body weight and body fat content.Testosterone could activate the NF-κB to pro-mote the expression of IL-6 and MCP-1. And testosterone facilitated to promote macro-phage to M1-subtype transformation.