ABOLISHING INCREASES IN INSULIN SENSITIVITY IN POSTMENOPAUSAL WOMEN

消除绝经后女性胰岛素敏感性的增加

• 批准号: 6263701
• 负责人: KATARINA T BORER
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6263701
• 关键词: adipose tissue; aging; clinical research; coronary disorder; disease /disorder proneness /risk; exercise; hormone biosynthesis; human subject; hypertension; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; obesity; postmenopause; women's health

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.

不活动和过量和不适当的热量摄入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身体脂肪损失的手段。 此外，运动，无论是否减肥，都可以降低糖尿病，高血压和冠心病的风险，但其效果并不一致。 特别是，关于运动强度对体脂减少、胰岛素敏感性或高血压和冠心病风险的影响，几乎没有共识。 我们的前提是，如果运动是有效地用于预防或减少不同的健康风险，或被用作激素作用的机械分析的工具，需要更好地了解运动强度的剂量依赖性影响。 我们的试点研究，开始于两年前，集中在高强度步行运动训练是否可以增加基础脉动生长激素（GH）分泌的问题。 我们的研究结果支持了这一假设（8，9），但此外，我们发现运动强度与体脂减少呈反比关系（通过间接人体测量方法评估），具有明显的致糖尿病效应（通过间接测量胰岛素敏感性评估），并与增加雄激素作用（血浆睾酮与性激素结合球蛋白的比率，SHBG）相关。 由于所有三个观察到的变化，内脏体脂肪的积累（6，44），GH过度分泌，和雄激素指数增加（47），或拮抗胰岛素的作用（GH分泌过多）或伴有糖尿病、高血压和CHD风险增加（高雄激素指数和餐后胰岛素反应增加），我们的研究结果表明，在15周的训练中，运动强度对至少两个危险因素有有害影响：它抑制了身体脂肪的减少和对胰岛素的外周敏感性。 这些偶然的观察结果将我们的兴趣从运动在缓解躯体疾病中的作用，自发GH分泌随年龄的指数下降，转移到运动强度影响绝经后妇女胰岛素抵抗、高血压和冠心病的机制。