TESTOSTERONE-INDUCED INSULIN INSENSITIVITY

高雄激素血症和胰岛素抵抗经常共存， 尽管这种关联的因果关系 不清楚 高雄激素血症可能导致 胰岛素不敏感性导致高胰岛素血症， 临床重要性增加。这一重大意义 源于流行病学报告， 高胰岛素血症伴动脉粥样硬化和冠状血管疾病。 检查雄激素对胰岛素敏感性的影响， 主要使用葡萄糖耐量试验。 我们的初步 研究已经利用了“钳”方法， 葡萄糖和胰岛素浓度处于预定水平，从而 最大限度地减少稳态反应，并允许评估 每个参数的影响。 在我们的研究中， 甲基睾酮的管理导致减少， 正常女性的胰岛素敏感性，当通过 正常血糖、高胰岛素钳夹技术或高血糖钳夹技术 钳位技术 此外，睾酮给药显著 正常血糖、高胰岛素血症期间犬的葡萄糖摄取减少 钳夹研究。 本协议将测试这三个建议的假设 研究，即睾丸激素诱导胰岛素不敏感性。 该提案将评估升高后的胰岛素敏感性， 降低人类和动物的睾酮水平。 的 使用的技术是l）正常血糖、高胰岛素钳夹 与3- 3 H-葡萄糖和L-[1 - 13 C]亮氨酸相关的研究 输液和间接量热法的性能，2） 高血糖钳夹程序和3）24小时全身热量测定 问题研究 将通过以下方法评估睾酮作用机制： 间接量热法测定葡萄糖和亮氨酸的命运 被肌肉吸收（氧化或储存）。最后这 该提案将研究存在的性别二态性， 睾酮降低胰岛素敏感性的能力， 女性，但男性的睾丸激素水平是女性的几倍， 高

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.