DIETARY DM

膳食DM

基本信息

批准号：
7608050
负责人：
DANIEL C STEIN
金额：
$ 1.68万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-15 至 2007-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7608050
关键词：
Area Arginine Beta Cell C-Peptide Cell physiology Computer Retrieval of Information on Scientific Projects Database Data Defect Dietary Fats Dose Drug Kinetics Dyslipidemias Emulsions Family suidae Fatty acid glycerol esters Functional disorder Funding Glucose Goals Grant Guidelines Heparin Hepatic Hepatocyte Hyperinsulinism Infusion procedures Institution Insulin Insulin Resistance Insulin, Aspart, Human Intake Link Lipids Magnetic Resonance Marines Medical Methods Monitor Muscle Fibers Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Obesity Oils Organ Peptides Plasma Procedures Protons Public Health Research Research Personnel Resources Risk Saturated Fatty Acids Scanning Source Spectrum Analysis Stable Isotope Labeling Structure of beta Cell of islet Study of magnetics Syndrome Testing Time Tissues Triglycerides United States National Institutes of Health Unsaturated Fats Vegetables animal data human subject in vivo insulin secretion lipid metabolism novel prevent saturated fat stable isotope

项目摘要

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. Increased availability of lipid substrates, particularly plasma non-esterified free fatty acids and intracellular triglyceride stores have been linked to many aspects of the insulin resistance syndrome including obesity, dyslipidemia and type 2 diabetes. Epidemiologic and animal data suggest that saturated fats have differential effects on the induction of insulin resistance as well as their effects (both stimulatory and inhibitory) on pancreatic beta cell function, particularly in comparison to unsaturated vegetable and marine oil fats. Current medical guidelines suggest limiting fat, particularly saturated fat intake. Surprisingly, considering the potential public health implications of dietary fat intake, little direct experimental data exists for human subjects in this area. The goal of these studies therefore, is to directly test the hypothesis that dietary saturated fatty acids time dependently both stimulate the insulin secretion more and then prevent compensatory insulin hypersecretion with prolonged exposure as compared to unsaturated fats using the novel method of in vivo stable isotope peptide pharmacokinetics. As beta cell hyperfunction decreases with prolonged NEFA exposure, hyperinsulinemia matching the degree of insulin resistance will be maintained by decreases in systemic and hepatic insulin clearance. We will also test the hypothesis that subjects at risk for Type 2 diabetes will be more sensitive to the effects of saturates compared to normal controls. Lastly we hypothesize that for the group as a whole, defects in insulin action, insulin clearance and finally beta cell secretory function will be closely paralleled by accumulations of intracellular triglycerides in multiple tissues including within hepatocytes and skeletal myocytes as monitored non-invasively by magnetic resonance proton spectroscopy and that this provides the unifying link to systemic organ dysfunction with abnormal lipid metabolism in the insulin resistance syndromes. Participating subjects will undergo the following procedures as part of this study: magnetic resonance scans, infusion of lipid emulsions i.v., infusion or heparin, stable isotope labeled glucose, lipids and C-peptide, insulins at low doses (porcine, insulin aspart, insulin-arginine).

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。脂质底物的可用性增加，尤其是血浆非酯化游离脂肪酸和细胞内甘油三酸酯储存库的可用性已与胰岛素抵抗综合征的许多方面联系在一起，包括肥胖，血脂异常和2型糖尿病。流行病学和动物数据表明，饱和脂肪对胰岛素抵抗的诱导以及它们对胰腺β细胞功能的影响（刺激性和抑制性）具有不同的影响，尤其是与不饱和蔬菜和海洋油脂相比。当前的医疗指南表明限制脂肪，尤其是饱和脂肪的摄入量。令人惊讶的是，考虑到饮食脂肪摄入的潜在公共卫生影响，该领域的人类受试者几乎没有直接的实验数据。因此，这些研究的目的是直接检验以下假设：与不饱和脂肪相比，使用体内稳定的同位素肽肽药物动力学相比，与不饱和脂肪相比，与不饱和脂肪相比，与长时间暴露相比，饮食饱和脂肪酸的时间依赖性依赖于胰岛素分泌，然后防止补偿性胰岛素超过分泌。随着β细胞的过度功能随长时间的NEFA暴露减少，与胰岛素抵抗程度相匹配的高胰岛素血症将通过系统性和肝胰岛素清除率的降低来维持。我们还将检验以下假设：与正常对照组相比，与2型糖尿病风险的受试者对饱和物的影响更敏感。 Lastly we hypothesize that for the group as a whole, defects in insulin action, insulin clearance and finally beta cell secretory function will be closely paralleled by accumulations of intracellular triglycerides in multiple tissues including within hepatocytes and skeletal myocytes as monitored non-invasively by magnetic resonance proton spectroscopy and that this provides the unifying link to systemic organ dysfunction with胰岛素抵抗综合征中的脂质代谢异常。参与的受试者将作为本研究的一部分进行以下程序：磁共振扫描，脂质乳液静脉注射，输注或肝素，稳定的同位素标记为葡萄糖，脂质和C肽，低剂量的胰岛素（猪，胰岛素疗法，胰岛素疗法，胰岛素 - 胰岛素 - 氨基氨酸）。