Effects of testosterone on insulin sensitivity in liver cells and related molecular mechanisms

Abstract

To explore the regulation of insulin sensitivity in liver cells by androgen signaling. Eleven adult female C57BL/6 mice were injected daily with testosterone (group T) for 24 weeks. And 10 control mice received sesame oil only (group Con). HepG2 liver cells were initially pretreated with different doses of testosterone (10(-9)-10(-5) mol/L ) for 0-36 h or with 10(-7) mol/L testosterone for 0-96 h followed by a stimulation of 100 nmol/L insulin for 15 min. Later HepG2 cells were pretreated with 10(-7) mol/L testosterone for 36 h followed by a stimulation of 100 nmol/L insulin for 15 min and then a restimulation of 100 nmol/L insulin for 15 min at 4 h and 6 h interval respectively. Phosphorylation and protein expression of Akt and GSK3β in C57BL/6 mice liver tissues and HepG2 cells were analyzed by Western blot. The 24-week treatment of testosterone decreased the phosphorylation of Akt and GSK3β in C57BL/6 adipose and liver tissues (43.1% ± 3.2% vs 77.1% ± 6.7%, 14.7% ± 6.7% vs 82.3% ± 2.0% respectively, P < 0.05). Pretreatment with 10(-8)-10(-6) mol/L testosterone within 36 h obviously increased the phosphorylation of Akt and GSK3β (P < 0.05). However pretreatment with 10(-5) mol/L within 36 h or with 10(-7) mol/L for 96 h had no effect on the phosphorylation of Akt and GSK3β compared with control group (P > 0.05). Pretreatment with 10(-7) mol/L testosterone for 36 h followed by insulin stimulation and restimulation after 6 h interval obviously decreased the phosphorylation of Akt and GSK3β (P < 0.05). Androgen signaling may contribute to insulin resistance in liver cells.