Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Mol Cell Biochem. 2011 Jun;352(1-2):35-45. doi: 10.1007/s11010-011-0737-1. Epub 2011 Feb 8.
Skeletal muscle, liver, and adipose tissue are major insulin responsive target organs that also express androgen receptor. Testosterone (T) plays a role in maintaining normal insulin sensitivity in men but its effects on insulin target tissues are not fully understood. Our previous study showed that orchidectomy impairs glucose oxidation through decreased insulin receptor (IR) mRNA expression in skeletal muscles, liver, and adipose tissue of male rat. Furthermore, T replacement restored IR mRNA expression in skeletal muscles and liver, but did not have any effect in adipose tissue. In the present study, orchidectomy decreased IR mRNA and protein levels in muscle, liver, and adipose tissue. Treatment with a combination of T plus estradiol (E) was necessary to restore the IR mRNA and protein to control levels in adipose tissue. T or E treatment alone had no effect on IR mRNA levels in adipose tissue. T alone also had no effect on the IR protein, whereas E alone had a stimulatory effect. In comparison, in muscle and liver, T or T plus E restored the IR mRNA and protein to control levels. In muscle and liver, E alone had no effect on IR mRNA expression but restored the IR protein. In addition, orchidectomy was seen to have a stimulatory effect on IRS-1 Serine(636/639) phosphorylation in the three tissues studied. Following T, E or combined supplementation to castrated rats, the pattern of IRS-1 serine phosphorylation was restored to normal control levels. Furthermore, orchidectomy decreased serum insulin and glucose oxidation in all three tissues, and this was restored by T and its combination with E replacement, whereas E alone had no effect. It is concluded from the present study that sex steroid deficiency induces impaired glucose oxidation in insulin responsive tissues, which is mediated through reduced IR expression, and increased IRS-1 serine phosphorylation.
骨骼肌、肝脏和脂肪组织是主要的胰岛素反应靶器官，也表达雄激素受体。睾丸酮（T）在维持男性的正常胰岛素敏感性方面发挥作用，但它对胰岛素靶组织的影响尚未完全了解。我们之前的研究表明，去势会通过降低雄性大鼠骨骼肌、肝脏和脂肪组织中胰岛素受体（IR）mRNA 的表达来损害葡萄糖氧化。此外，T 替代物可恢复骨骼肌和肝脏中的 IR mRNA 表达，但对脂肪组织没有任何作用。在本研究中，去势降低了肌肉、肝脏和脂肪组织中的 IR mRNA 和蛋白水平。T 加雌二醇（E）联合治疗是必需的，以将 IR mRNA 和蛋白恢复到脂肪组织的对照水平。T 或 E 单独治疗对脂肪组织中的 IR mRNA 水平没有影响。T 单独治疗对 IR 蛋白也没有影响，而 E 单独治疗则有刺激作用。相比之下，在肌肉和肝脏中，T 或 T 加 E 将 IR mRNA 和蛋白恢复到对照水平。在肌肉和肝脏中，E 单独治疗对 IR mRNA 表达没有影响，但可恢复 IR 蛋白。此外，去势对所研究的三种组织中的 IRS-1 丝氨酸（636/639）磷酸化有刺激作用。在给予去势大鼠 T、E 或联合补充后，IRS-1 丝氨酸磷酸化模式恢复到正常对照水平。此外，去势降低了三种组织中的血清胰岛素和葡萄糖氧化，这可通过 T 及其与 E 的联合替代来恢复，而 E 单独治疗则没有作用。综上所述，本研究表明，性激素缺乏会导致胰岛素反应组织中葡萄糖氧化受损，这是通过降低 IR 表达和增加 IRS-1 丝氨酸磷酸化来介导的。
