ABOLISHING INCREASES IN INSULIN SENSITIVITY IN POSTMENOPAUSAL WOMEN

缺乏运动和过量和不适当的卡路里摄入会刺激内脏肥胖的发展，这与2型(非胰岛素依赖型)糖尿病、高血压和冠心病(CHD)的风险增加有关。运动和饮食限制都被成功地用作减肥的一种手段。此外，运动，无论是否减脂，都可以降低患糖尿病、高血压和冠心病的风险，但其效果并不一致。特别是，关于运动强度对身体脂肪减少、胰岛素敏感性或高血压和冠心病风险的影响，几乎没有达成共识。我们的前提是，如果要有效地利用运动来预防或减少不同的健康风险，或者将其用作激素作用的机械分析工具，就需要更好地理解运动强度的剂量依赖效应。我们的初步研究始于两年前，重点是高步行强度的运动训练是否可以增加基础脉搏生长激素(GH)的分泌。这一假设得到了我们的结果(8，9)的支持，但此外，我们还发现，运动强度与身体脂肪减少呈负相关(通过间接的人体测量法评估)，具有明显的促糖尿病作用(通过间接衡量胰岛素敏感性)，并与增加雄激素的作用(血浆睾酮与性激素结合球蛋白的比率，SHBG)有关。由于所有三个观察到的变化，内脏脂肪积累(6，44)，GH过度分泌，雄激素指数增加(47)，要么拮抗胰岛素作用(GH过度分泌)，要么伴有糖尿病、高血压和冠心病风险增加(高雄激素指数和餐后胰岛素反应增加)，我们的结果表明，15周的运动强度对至少两个危险因素有有害影响：抑制身体脂肪减少和外周胰岛素敏感性。这些偶然的观察将我们的兴趣从运动在缓解躯体更年期中的作用，即随年龄增长的自发性生长激素分泌指数下降，转向运动强度影响绝经后女性胰岛素抵抗、高血压和冠心病的机制。

Inactivity and excessive and inappropriate caloric intake stimulate development of visceral obesity that is associated with increased risks of type 2 (non-insulin-dependent) diabetes, hypertension, and coronary heart disease (CHD). Both exercise and dietary restriction have been successfully used as a means of body fat loss. In addition, exercise, with or without fat loss, can reduce risks of diabetes, hypertension, and coronary heart disease but its effects have not been consistent. In particular, there is little consensus regarding the effects of exercise intensity on either body fat loss, insulin sensitivity, or risks of hypertension and CHD. Our premise is that if exercise is to be used effectively to prevent or reduce different health risks or to be used as a tool in mechanistic analyses of hormone action, a better understanding of dose-dependent effects of exercise intensity is needed. Our pilot study, initiated two years ago, focused on the question of whether exercise training at high walking intensities could increase basal pulsatile growth hormone (GH) secretion. This hypothesis was supported by our results (8,9), but in addition, we discovered that exercise intensity bears an inverse relationship to body fat loss (assessed by indirect, anthropometric methods), has an apparent diabetogenic effect (assessed with an indirect measure of insulin sensitivity), and is associated with increased androgenic action (ratio of plasma testosterone to sex-hormone-binding globulin, SHBG). Since all three observed changes, the accumulation of visceral body fat (6,44), GH oversecretion, and increased androgenic index (47), either antagonize insulin action (GH oversecretion) or are accompanied by increased risk of diabetes, hypertension, and CHD (high androgenic index and increased postprandial insulin response), our results suggested that exercise intensity during 15 weeks of training had a deleterious effect on at least two risk factors: it was inhibitory to body fat loss and to peripheral sensitivity to insulin. These serendipitous observations redirected our interest from the role of exercise in alleviating somatopause, the exponential decline in spontaneous GH secretion with age, to the mechanism by which exercise intensity affects insulin resistance, hypertension and CHD in postmenopausal women.