DIETARY SALT INTAKE AND THE METABOLIC EFFECTS OF INSULIN

膳食盐摄入量和胰岛素的代谢影响

• 批准号: 6516734
• 负责人: Raymond R Townsend
• 金额: $ 11.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6516734
• 关键词: African American; calorimetry; caucasian American; clinical research; dietary sodium; fatty acids; glucose clamp technique; human subject; insulin; insulin sensitivity /resistance; lipid metabolism; norepinephrine; renin angiotensin system; salt intake; sympathetic nervous system

DESCRIPTION (taken from the application) The hemodynamic and metabolic effects of insulin make it an ideal hormone to facilitate the delivery and storage of ingested nutrient. Impaired tissue blood flow can reduce glucose uptake by insulin (insulin resistance) and the compensatory hyperinsulinemia has been implicated in the pathogenesis of hyperlipidemia and atherosclerosis. Insulin resistance is associated with activation of the renin-angiotensin and adrenergic nervous systems which can reduce blood flow. Increasing salt intake suppresses activity of both of these systems and may improve insulin sensitivity, but recent studies of this issue are conflicting since studies used different techniques to evaluate insulin sensitivity, were limited to men, and did not compare responses among diverse ethnic groups. The advice to reduce salt intake has important health consequences if salt restriction has adverse metabolic consequences such as a reduction in insulin sensitivity. I have recently shown a significant negative correlation between plasma renin activity and insulin sensitivity, and I hypothesize that high dietary salt intake increases insulin-sensitive glucose transport when compared to a low salt intake. I will test this single hypothesis through three Specific Aims by examining 1) the effects of 1 week isocaloric Low (20 meq sodium) versus 1 week of a High (230 meq) salt intake in Caucasian and African/American men/women using the euglycemic clamp to assess insulin sensitivity; 2) the effect of insulin infusion on leg blood flow using impedance plethysmography on different salt intakes, and 3) the mechanism by which increased salt intake elevates fatty acid concentration by demonstrating an increase in lipolysis rate on High Salt intake, measured by the stable isotope deuterated glycerol coupled with indirect calorimetry measurements to assess fatty acid oxidation on the Low and High salt intakes. Activity of the renin-angiotensin and (indirectly) the adrenergic nervous systems will be evaluated by determining plasma renin activity and plasma/urinary norepinephrine concentrations at the end of each dietary salt phase. Statistical significance of the insulin sensitivity data will be evaluated by paired t-testing. If increased salt intake improves insulin sensitivity this should prompt a re-evaluation of the benefits of recommending a lower sodium intake in normotensive people.

描述（取自应用程序） 胰岛素的血液动力学和代谢作用使其成为理想的激素， 促进摄入的营养素的输送和储存。组织血液受损 血流可以减少胰岛素对葡萄糖的摄取（胰岛素抵抗）， 代偿性高胰岛素血症与糖尿病的发病机制有关， 高脂血症和动脉粥样硬化。胰岛素抵抗与 激活肾素-血管紧张素和肾上腺素能神经系统， 减少血液流动。增加盐的摄入会抑制这两种活性 系统，并可能改善胰岛素敏感性，但最近的研究，这个问题 由于研究使用不同的技术来评估胰岛素， 敏感性，仅限于男性，并没有比较不同的反应， 种族群体。减少盐摄入量的建议对健康有重要意义 如果限盐会产生不利的代谢后果， 胰岛素敏感性降低。我最近表现出了明显的负面影响 血浆肾素活性与胰岛素敏感性的相关性，以及I 假设高饮食盐摄入增加胰岛素敏感性葡萄糖 与低盐摄入量相比，我会测试这首单曲 通过检查1）1周的影响，通过三个具体目标的假设 等热量低（20 meq钠）与1周高（230 meq）盐摄入， 高加索和非洲/美国男性/女性，使用正葡萄糖钳夹法评估 胰岛素敏感性; 2）胰岛素输注对腿部血流的影响， 阻抗体积描记法对不同盐摄入量的影响，以及3） 盐摄入量的增加会提高脂肪酸浓度， 高盐摄入量的脂解率增加，通过稳定的 同位素氘代甘油与间接量热测量相结合， 评估脂肪酸氧化对低盐和高盐摄入的影响。活性 肾素-血管紧张素和（间接）肾上腺素能神经系统将 通过测定血浆肾素活性和血浆/尿液进行评估 每个饮食盐阶段结束时的去甲肾上腺素浓度。 胰岛素敏感性数据的统计学显著性将通过 配对t检验如果增加盐的摄入量可以改善胰岛素敏感性， 应该促使人们重新评估推荐低钠饮食的好处， 正常血压人群的摄入量。