CARBOHYDRATE METABOLISM AND CATECHOLAMINES

应用程序的长期目标是确定 胰岛素与交感神经系统(SNS)在糖尿病发病机制中的作用 肥胖相关的高血压。具体目标是：1)确定 肥胖性高血压患者交感神经活性水平的比较 血压正常的肥胖受试者和临时体重控制正常的人 状态；2)确定高胰岛素血症(胰岛素)与 抵抗力)、SNS活性和血压(BP)与肥胖相关 3)建立肥胖相关高血压大鼠模型 基于长期服用高脂肪饮食；以及4)确定 胰岛素与三七总皂苷、三七总皂苷与血压的关系 肥胖相关的高血压。在人类受试者中，评估了SNS的活性 测定血浆去甲肾上腺素(NE)、尿去甲肾上腺素 排泄物，和 从示踪剂计算出的NE在循环中的出现率 动力学实验。在大鼠中，SNS的活性在心脏，肾脏， 白色脂肪组织、棕色脂肪组织和肝脏通过测量 NE周转率在人和大鼠这些器官中的关系 胰岛素和SNS之间的关系，而SNS和BP将由 比较改变胰岛素抵抗和/或干预措施的影响 循环胰岛素水平对SNS活性和血压的影响。干预措施 在人类中的应用包括：一种快速修饰的蛋白质；输注 长效生长抑素类似物治疗生长抑素 (奥曲肽，善得定)；一种正常血糖的高胰岛素葡萄糖钳。 在脂肪喂养的大鼠中，干预措施包括补充鱼油；燕麦麸皮 补充剂；链脲佐菌素诱导的实验性糖尿病；治疗 使用奥曲肽。2-脱氧葡萄糖对大鼠交感神经的影响 脂肪喂养的动物的活动和血压也将被评估为与肥胖有关 高血压是#年心血管疾病发病率和死亡率的主要原因。 肥胖者。尽管高胰岛素血症与高血压有关 这组人的心血管风险，胰岛素作用于 影响血压和心血管系统的机制尚未建立。这个 本申请中提出的研究将评估 胰岛素介导的交感神经刺激在高血压发病机制中的作用 肥胖相关的高血压。澄清所涉及的机制 重要的治疗意义和产生有利影响的潜力 肥胖者中心血管疾病的发病率很高。

The long-term goals of the application are to determine the role played by insulin and the sympathetic nervous system (SNS) in the pathogenesis of obesity-relate hypertension. The specific aims are: 1) to determine the level of sympathetic activity in obese hypertensive subjects as compared with obese normotensive subjects and normal weight controls in the ad lib state; 2) to determine the relationships between hyperinsulinemia (insulin resistance), SNS activity, and blood pressure (BP) in human obesity-related hypertension; 3) to develop a rat model of obesity-related hypertension based on the chronic administration of a high fat diet; and 4) to determine the between insulin and the SNS, and the SNS and BP in the rat model of obesity-related hypertension. In human subjects, SNS activity is assessed by measurements of plasma norepinephrine (NE) concentration, urinary NE excretion, and the rate of appearance of NE in the circulation as calculated from tracer kinetic experiments. In rats SNS activity is assessed in heart, kidney, white adipose tissue brown adipose tissue, and liver by the measurement of NE turnover rate in these organs In humans and rats the relationship between insulin and the SNS, and the SNS and BP will determined by comparing the impact of interventions that alter insulin resistance and/or the level of circulating insulin on SNS activity and BP. The intervention utilized include, in humans: a protein sparing modified fast; infusion of somatostatin treatment with a long acting somatostatin analogue (octreotide, Sandostatin); an euglycemic hyperinsulinemic glucose clamps. In fat fed rats the interventions include fish oil supplements; oat bran supplements; experimental diabetes induced by streptozotocin; treatment with octreotide. In rats the effect of 2-deoxyglucose on sympathetic activity and BP in fat fed animals will be assessed as well obesity-related hypertension is a major cause of cardiovascular morbidity and mortality in the obese. Although hyperinsulinemia has been linked with hypertension cardiovascular risk in this group, the mechanisms by which insulin acts to affect BP an the cardiovascular system have not been established. The studies proposed in this application will assess the role of insulin-mediated sympathetic stimulation in the pathogenesis of obesity-related hypertension. Clarification of the mechanisms involved has important therapeutic implications and the potential to impact favorably the cardiovascular morbidity prevalent in the obese.