SEX HORMONES, FAT DISTRIBUTION AND THE METABOLIC PROFILE

这个应用程序的目的是定义性别的作用 激素平衡与体脂分布的关系 高胰岛素血症、葡萄糖耐受不良和胰岛素抵抗 绝经前妇女 我们建议验证一个代谢 序列中增加雄激素活性可能导致 脂肪在上身的定位和肝脏的下降 胰岛素提取和胰岛素敏感性。 我们假设， 女性肝脏和局部脂肪细胞前体对 雄激素和雌激素的平衡 之敏感度 雄激素在女性是加剧了异常的性行为 胰岛素和糖代谢紊乱 肥胖症的存在进一步加剧了这种情况。 我们首先 评估与性激素分布和体脂相关的机制 葡萄糖-胰岛素稳态不依赖性缺陷 肥胖症。 为此，正常、肥胖和前肥胖 不同体脂分布的绝经前妇女， 检查以确定：i）肝前产生和肝 胰岛素的提取，ii）胰岛素调节的葡萄糖产生; 外周葡萄糖利用、氧化和储存;以及脂解， 和iii）骨骼肌形态和敏感性。 然后我们 评估高雄激素性对 内脏胰岛素代谢和胰岛素作用，独立于 通过研究正常体重和中度肥胖 高雄激素化妇女改善前和改善后， 高雄激素状态 最后，我们解开了 雄激素影响局部脂肪的机制 组织生长和肝脏胰岛素代谢。 的关系 雄激素活性区域前脂肪细胞分化和 肝细胞胰岛素代谢检查性二型 大鼠，实验诱导性畸变的雌性大鼠 二型性和缺乏雄激素受体的大鼠。 这 方向扩展了目前的科学数据，从我们的 并应揭示复杂的病理生理机制 身体脂肪分布和葡萄糖之间的关系 不耐受和非胰岛素依赖型糖尿病。

The objective of this application is to define the role of sex hormone balance in the association between body fat distribution and hyperinsulinemia, glucose intolerance and insulin resistance in premenopausal women. We propose to validate a metabolic sequence in which increased androgenic activity could lead to localization of fat in the upper body and to a decline in hepatic insulin extraction and insulin sensitivity. We postulate that the female liver and regional adipocyte precursors are highly sensitive to the androgenic:estrogenic balance. The sensitivity to androgens in the female is exacerbated by aberrant sexual dimorphism and the disturbance in insulin and glucose metabolism is further exacerbated by the presence of obesity. We first evaluate mechanisms relating sex hormone profiles and body fat distribution to defects in glucose-insulin homeostasis independent of obesity. For this purpose, normal, obese and ex-obese premenopausal women of varying body fat distribution are examined to determine: i) prehepatic production and hepatic extraction of insulin, ii) insulin-regulated glucose production; peripheral glucose utilization, oxidation and storage; and lipolysis, and iii) skeletal muscle morphology and sensitivity. We then assess the contribution of hyperandrogenicity to defects in splanchnic insulin metabolism and insulin action, independent of obesity by studying normal weight and moderately obese hyperandrogenized women before and after amelioration of the hyperandrogenic state. Finally, we unravel the cellular mechanisms by which androgenes could influence regional adipose tissue growth and hepatic insulin metabolism. The relationship of androgenic activity to regional preadipocyte differentiation and hepatocyte insulin metabolism is examined in sexually dimorphic rats, female rats with experimentally induced aberrant sexual dimorphism, and rats lacking the androgen receptor. This direction extends the current body of scientific data from our group and should reveal the complex pathophysiologic mechanisms underlying the relationship of body fat distribution, to glucose intolerance and non-insulin dependent diabetes mellitus.