TESTOSTERONE-INDUCED INSULIN INSENSITIVITY

高雄激素症和胰岛素抵抗经常共存， 尽管这种关联的因果关系是 不清楚。高雄激素症可能会导致 胰岛素不敏感，导致高胰岛素血症，已经成为 临床重要性的增加。这一高度的意义 源于流行病学报告，表明 高胰岛素血症合并动脉粥样硬化和冠状动脉血管疾病。 研究雄激素对胰岛素敏感性的影响 主要用于葡萄糖耐量试验。我们的预赛 研究已经使用了“钳位”方法固定葡萄糖或 葡萄糖和胰岛素浓度处于预定水平，从而 最大限度地减少动态平衡反应，并允许评估 每个单独参数的影响。在我们的研究中， 服用甲基睾丸素可导致 正常女性的胰岛素敏感性，当用 正常血糖、高胰岛素钳夹技术或高血糖 钳夹技术。此外，睾丸素的使用明显 正常血糖、高胰岛素血症时狗的葡萄糖摄取减少 夹具研究。 这个方案将检验这三个人提出的假设 研究表明，睾丸激素会导致胰岛素不敏感。 该提案将在胰岛素升高或升高后评估胰岛素敏感性 降低人类和动物体内的睾丸素水平。这个 可采用的技术有：(L)正血糖、高胰岛素钳夹 3-3H-葡萄糖和L-[L-13C]亮氨酸的研究 输液与间接量热法的性能，2) 高血糖钳夹手术和3)24小时全身热量测量 学习。睾酮的作用机制将通过以下方式进行评估 间接量热法测定葡萄糖和亮氨酸的去向 被肌肉吸收(氧化或储存)。最后，这一点 提案将审查存在的性别二形性 睾丸激素降低胰岛素敏感性的能力 女性，但不是男性，因为男性的睾丸素水平是男性的几倍 再高一点。

Hyperandrogenism and insulin resistance frequently coexist, although the cause and effect relationship of this association is not clear. The possibility that hyperandrogenism may induce insulin insensitivity, with resultant hyperinsulinemia, has become of increased clinical importance. This heightened significance stems from epidemiologic reports suggesting a link of hyperinsulinism with atherosclerosis and coronary vascular disease. Examination of the effect of androgens on insulin sensitivity has primarily utilized glucose tolerance testing. Our preliminary studies have utilized "clamp" methodologies which fix glucose or glucose and insulin concentrations at predetermined levels, thereby minimizing homeostatic responses and allowing evaluation of the effect of each individual parameter. In our studies, methyltestosterone administration resulted in a reduction in insulin sensitivity in normal women, when assessed either by the euglycemic, hyperinsulinemic clamp technique or the hyperglycemic clamp technique. Furthermore, testosterone administration markedly reduced glucose uptake in dogs during euglycemic, hyperinsulinemic clamp studies. This protocol will test the hypothesis suggested by these three studies, namely that testosterone induces insulin insensitivity. The proposal will evaluate insulin sensitivity after elevation or reduction of testosterone levels in humans and animals. The techniques to be utilized are l) euglycemic, hyperinsulinemic clamp studies in association with 3-3H-glucose and L-[l-13C)leucine infusion and the performance of indirect calorimetry, 2) hyperglycemic clamp procedures, and 3) 24h whole body calorimetry studies. The mechanism of testosterone action will be assessed by indirect calorimetry to determine the fate of glucose and leucine taken up by muscle (either oxidation or storage). Lastly, this proposal will examine the sexual dimorphism that exists with regard to the ability of testosterone to reduce insulin sensitivity in women, but not in men in whom testosterone levels are several-fold higher.