REGULATION OF FFA METABOLISM IN NORMAL AND DIABETIC MAN

这项研究将继续在该地区的监管脂解 和人体内的游离脂肪酸氧化。 了一个极为精确 高效液相色谱法 血浆棕榈酸酯浓度和特异性 活动已经制定，其准确性得到验证。 的 拟议的研究将系统地调查激素和 调节脂解和游离脂肪酸的底物因子 氧化，使用“胰腺钳”技术。 而 关于这一主题的广泛的体外信息是可用的， 调节动员的激素和底物因子 和游离脂肪酸的氧化仍有待确定。 的 该提案最初将侧重于剂量-反应关系 胰岛素利用率和游离脂肪酸动员之间的关系， 在输注胰岛素期间的氧化， 循环血浆浓度在5 - 50 Mu/ml之间。 对 根据这些实验的结果， 率将被选择用于后续研究， 评估分级高血糖和增量血糖的影响， 在生理范围内增加肾上腺素， 激素，胰高血糖素和皮质醇在正常人和胰岛素- 依赖性糖尿病患者 具体而言，这些研究将1）确定 无论是脂解的敏感性和/或反应性， 脂肪酸氧化在胰岛素控制不佳的情况下减少， 依赖性糖尿病; 2）确定高血糖本身是否 抑制正常人和哺乳动物中的脂解和/或游离脂肪酸氧化， 糖尿病男性; 3）确定是否敏感性和 脂肪分解和游离脂肪酸氧化对 肾上腺素正常或在控制不佳的糖尿病中增加; 4)确定是否生长激素过量增加脂解 正常人和糖尿病人的游离脂肪酸氧化; 5） 确定胰高血糖素是否刺激脂解和游离脂肪酸 正常人和糖尿病人中的酸氧化;以及6）测定 高皮质醇血症是否会增加正常人的脂解 以及糖尿病控制不佳的患者。 这些研究将 为游离脂肪酸的控制提供了新的见解 在体内代谢，并将导致更多的研究， 底物和激素相互作用在调节 人体的燃料代谢

This research will continue in the area of regulation of lipolysis and free fatty acid oxidation in humans. An extremely precise and accurate high performance liquid chromatographic method for the determination of plasma palmitate concentration and specific activity has been developed and its accuracy validated. The proposed studies will systematically investigate the hormonal and substrate factors which regulate lipolysis and free fatty acid oxidation, using the "pancreatic clamp" technique. While extensive in vitro information on this subject is available, the hormone and substrate factors which regulate the mobilization and oxidation of free fatty acids remain to be determined. The proposal will focus initially on the dose-response relationship between insulin availability and free fatty acid mobilization and oxidation during infusion of insulin at rates which will achieve circulating plasma concentrations between 5 and 50 Mu/ml. On the basis of the results from these experiments, an insulin infusion rate will be selected for subsequent studies to independently assess the effects of graded hyperglycemia and incremental increases, within the physiologic range, of epinephrine, growth hormone, glucagon and cortisol in normal subjects and insulin- dependent diabetics. Specifically, these studies will 1) determine whether the sensitivity and/or responsiveness of lipolysis and free fatty acid oxidation is reduced in poorly controlled insulin- dependent diabetes; 2) determine whether hyperglycemia per se inhibits lipolysis and/or free fatty acid oxidation in normal and diabetic man; 3) determine whether the sensitivity and responsiveness of lipolysis and free fatty acid oxidation to epinephrine is normal or increased in poorly controlled diabetes; 4) determine whether growth hormone excess increases lipolysis and free fatty acid oxidation in normal and diabetic man; 5) determine whether glucagon stimulates lipolysis and free fatty acid oxidation in normal and diabetic man; and 6) determine whether hypercortisolemia increases lipolysis in normal subjects and patients with poorly controlled diabetes. These studies will provide new insights into the control of free fatty acid metabolism in vivo and will lead to additional studies of the effect of substrate and hormonal interactions in the regulation of fuel metabolism in man.