REGULATION OF NUTRIENT METABOLISM IN MALES AND FEMALES

此申请的目的是确保资金，将提供指定PI的工资支持。申请的理由是基于申请人从学生到博士后研究员到助理教授的进展。这一进展最近导致获得了大量外部资金和独立调查员地位。K 02奖将为申请人提供必要的资金，以实现她的短期和长期目标，分别是;进一步发展她的研究专业知识，出版记录和研究资金;并成为一个既定的研究者，具有强大的独立研究计划。候选人在科罗拉多大学健康科学中心的职位，使她在一个良好的环境中发展她的研究生涯。重要的资源包括一般临床研究中心，临床营养研究单位和人类营养中心。本申请中提出的研究旨在更好地了解与发育和/或预防疾病有关的代谢的性别差异。具体目标#1将确定肾上腺素和去甲肾上腺素对雄性和雌性动物脂解速率和葡萄糖生成的影响。这将利用胰腺钳夹技术结合儿茶酚胺输注和稳定同位素测量。具体目标#$2将确定男性和女性从循环中清除外源性脂质的能力是否存在差异，以及胰岛素抑制内源性极低密度脂蛋白甘油三酯（VLDL-TG）和VLDL载脂蛋白-B（apo B）分泌的能力是否存在性别差异。将根据静脉脂肪耐量试验评估脂质清除率。在VLDL-TG放射性标记和肝脏apo B稳定同位素标记后，将测量VLDL-TG和apo B分泌的相对变化。将在基础和高胰岛素血症-血糖正常条件下测量VLDL-TG和apo B动力学。具体目标#3将确定急性运动对膳食脂质和碳水化合物代谢影响的性别差异。这将通过在液体膳食中添加放射性和稳定同位素并在餐后示踪剂和营养分配（无论是否进行运动）后实现。这些研究将进一步加深我们对男性和女性疾病的代谢基础的理解，并开始确定干预措施的性别特异性影响。

The purpose of this application is to secure funding that will provide salary support for the named PI. The rationale for the application is based on the applicants demonstrated progression from student to Post-doctoral Fellow to Assistant Professor. This Progression has recently resulted in the acquisition of significant external funding and independent investigator status. The K02 Award will provide the applicant with the necessary funding to achieve both her short- and long-term goals which are respectively; to further develop her research expertise, publication record, and research funding; and to become an established investigator, with a strong independent research program. The candidates position at the University of Colorado Health Sciences Center, places her in an excellent environment to develop her research career. Important resources include the General Clinical Research Center, Clinical Nutrition Research Unit and Center for Human Nutrition. The studies proposed in this application aim to better understand gender differences in metabolism that relate to the development and/or protection against disease. Specific Aim #1 will determine the effects of epinephrine and norepinephrine on rates of lipolysis and glucose production in males and females. This will utilize the pancreatic clamp technique in conjunction with catecholamine infusions and stable isotope measurements. Specific Aim #$2 will determine if males and females differ in their ability to remove exogenous lipid from the circulation and whether there are gender differences in the ability of insulin to suppress endogenous very-low density lipoprotein triglyceride (VLDL-TG) and VLDL apolipoprotein-B (apo B) secretion,. Lipid clearance will be assessed in response to an intravenous fat tolerance test. Relative changes in VLDL-TG and apo B secretion will be measured following the radioactive labeling of VLDL-TG and stable isotope labeling of hepatic apo B. Measurement of VLDL-TG and apo B kinetics will be made under basal and hyperinsulinemic-euglycemic conditions. Specific Aim #3 will determine gender differences in the effects of acute exercises on meal lipid and carbohydrate metabolism. This will be achieved by the addition of radioactive and stable isotopes to a liquid meal and follow post-prandial tracer and nutrient partitioning, with and without, preceding exercise. These studies will further our understanding of the metabolic basis for disease in males and females and begin to identify gender specific effects of interventions.