ARGININE AND INSULIN SENSITIVITY

精氨酸和胰岛素敏感性

• 批准号: 7950656
• 负责人: Leticia Castillo
• 金额: $ 3.64万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950656
• 关键词: Adolescent; Amino Acids; Animal Model; Animals; Arginine; Blood flow; Child; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Dyslipidemias; Euglycemic Clamping; Fatty Acids; Fatty acid glycerol esters; Functional disorder; Funding; Glucose; Glucose Clamp; Glycerol; Grant; Health; Hyperlipidemia; Hypertension; Infusion procedures; Institution; Insulin; Insulin Resistance; Intake; Intravenous; Leucine; Lymphocyte; Mammals; Mediator of activation protein; Nitric Oxide; Nitric Oxide Synthase; Obesity; Oral; Overweight; PPAR gamma; Palmitates; Pathogenesis; Rattus; Research; Research Personnel; Resources; Role; Source; Supplementation; Tissues; Tracer; United States National Institutes of Health; cardiovascular risk factor; cell type; diabetic; glucose metabolism; improved; insulin sensitivity; monocyte; protein degradation; protein metabolism; uptake; Adolescent; Amino Acids; Animal Model; Animals; Arginine; Blood flow; Child; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Dyslipidemias; Euglycemic Clamping; Fatty Acids; Fatty acid glycerol esters; Functional disorder; Funding; Glucose; Glucose Clamp; Glycerol; Grant; Health; Hyperlipidemia; Hypertension; Infusion procedures; Institution; Insulin; Insulin Resistance; Intake; Intravenous; Leucine; Lymphocyte; Mammals; Mediator of activation protein; Nitric Oxide; Nitric Oxide Synthase; Obesity; Oral; Overweight; PPAR gamma; Palmitates; Pathogenesis; Rattus; Research; Research Personnel; Resources; Role; Source; Supplementation; Tissues; Tracer; United States National Institutes of Health; cardiovascular risk factor; cell type; diabetic; glucose metabolism; improved; insulin sensitivity; monocyte; protein degradation; protein metabolism; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity and its associated insulin resistance are an important health problem in children. Recent studies have identified Nitric Oxide (NO) as a mediator in the pathogenesis of insulin resistance. Arginine is the single precursor for NO and arginine supplementation has improved insulin resistance and dyslipidemia in animal models, possibly through the expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) coactivator-1alpha. This study seeks to determine the effect of L-arginine supplementation on insulin resistance and energy and protein metabolism in obese adolescents. HYPOTHESIS: Arginine supplementation to obese adolescents will improve insulin sensitivity, dyslipidemia and protein turnover in these subjects. SPECIFIC AIMS: To assess the effect of a 7 day oral supplementation with 300mg/kg/day of L-arginine on insulin sensitivity in overweight and obese adolescents by conducting a 7hour, constant intravenous tracer infusion of L-[5,5,2H2] leucine, [13C] glucose, [2H5] glycerol, and [2H2]palmitate at baseline, and during a Hyperinsulinemic Euglycemic Clamp (HEC). To investigate the expression of PPAR-gamma in lymphocytes of obese and overweight adolescents and healthy controls, at baseline and during arginine supplementation. BACKGROUND AND SIGNIFICANCE: Obesity and its associated insulin resistance are becoming an important health concern in children. Among the main features of obesity is increased insulin resistance with a higher cardiovascular risk including hypertension, diabetes, hyperlipidemia, etc. Insulin resistance is associated with endothelial dysfunction, and recent studies have identified an important role for Nitric oxide in the pathogenesis of insulin resistance. Nitric oxide (NO) is synthesized from L-arginine by NO synthase in virtually all cell types. Emerging evidence shows that NO regulates the metabolism of glucose, fatty acids and amino acids in mammals. Previous studies have shown that an inhibition of NO synthesis causes hyperlipidemia and fat accretion in rats, whereas dietary arginine supplementation reduces fat mass in diabetic fatty rats. Among the mechanisms that explain these findings in animal studies include: NO activates the expression of peroxisome proliferator-activated receptor gamma;PPAR-gamma coactivator-1alpha, NO increases blood flow to insulin-sensitive tissues, promoting substrate uptake. Arginine supplementation has improved insulin resistance in animal models. This study seeks to evaluate the effect of L-arginine supplementation in energy and protein metabolism, insulin resistance and the expression of peroxisome proliferator-activated receptor-gamma in monocytes of obese adolescents, under basal conditions and during a hyperinsulinemic euglycemic clamp (HEC) during their usual intake and during dietary arginine supplementation for 14 days.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 肥胖及其相关的胰岛素抵抗是儿童的重要健康问题。最近的研究已将一氧化氮（NO）确定为胰岛素抵抗发病机理的介体。精氨酸是NO的单一前体，补充精氨酸可以改善动物模型中的胰岛素抵抗和血脂异常，这可能是通过过氧化物酶体增殖物激活的受体伽马（PPAR-GAMMA）共激活剂-1alpha的表达。这项研究旨在确定肥胖青少年中补充L-精氨酸对胰岛素抵抗，能量和蛋白质代谢的影响。 假设：补充肥胖青少年的精氨酸将改善这些受试者的胰岛素敏感性，血脂异常和蛋白质更新。 SPECIFIC AIMS: To assess the effect of a 7 day oral supplementation with 300mg/kg/day of L-arginine on insulin sensitivity in overweight and obese adolescents by conducting a 7hour, constant intravenous tracer infusion of L-[5,5,2H2] leucine, [13C] glucose, [2H5] glycerol, and [2H2]palmitate at baseline, and during高胰岛素的葡萄糖夹（HEC）。 在基线和补充精氨酸期间，研究肥胖和超重青少年和健康对照的淋巴细胞中PPAR-GAMMA的表达。 背景和意义： 肥胖及其相关的胰岛素抵抗正在成为儿童的重要健康问题。肥胖的主要特征之一是增加胰岛素抵抗性，具有较高的心血管风险，包括高血压，糖尿病，高脂血症等。胰岛素抵抗与内皮功能障碍有关，最近的研究确定了一氮氧化物在胰岛素抵抗病原体中的重要作用。 一氧化氮（NO）在几乎所有细胞类型中通过NO合酶从L-精氨酸中合成。新兴的证据表明，没有调节哺乳动物中葡萄糖，脂肪酸和氨基酸的代谢。先前的研究表明，对NO合成的抑制作用会引起大鼠高脂血症和脂肪的积聚，而饮食精氨酸的补充减少了糖尿病脂肪大鼠的脂肪量。在动物研究中解释这些发现的机制中包括：NO激活过氧化物酶体增殖物激活的受体伽马的表达； PPAR-GAMMA共激活剂-1Alpha，没有增加血液流向胰岛素敏感的组织，从而促进了底物的摄取。在动物模型中，补充精氨酸可以提高胰岛素抵抗。 这项研究旨在评估补充L-精氨酸在能量和蛋白质代谢，胰岛素抵抗以及在肥胖青少年的单核细胞中，在基础胰岛素血症血症乳液（HEC）和日粮期间，在肥胖青少年的单核细胞中，过氧化物酶体增殖物激活的受体伽马表达在肥胖青少年的单核细胞中的作用。