EXTREME DIETARY CARBOHYDRATE RESTRICTION EFFECT ON HEPATIC GLUCOSE PRODUCTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。肥胖及其相关的合并症是21世纪医学界面临的最普遍和最具挑战性的疾病之一。从历史上看，美国国立卫生研究院目前提出的减肥饮食建议很难启动和维持。此外，糖尿病患者的推荐饮食已被证明在短期内有效，但在帮助血糖控制方面长期不足。最近流行的碳水化合物限制饮食可能比低脂肪、高碳水化合物、限制卡路里的饮食更有利于那些寻求减肥和改善血糖控制的人。然而，人们对这两种饮食对肝脏葡萄糖代谢的影响知之甚少。本研究旨在确定严格限制饮食碳水化合物对肝脏葡萄糖代谢的影响，包括肝脏产生的葡萄糖前体（糖原、甘油和丙酮酸）的来源，以及中间体通过克雷布斯循环、腓尼基后丙酮酸羧激酶和丙酮酸再循环的通量。识别肝脏葡萄糖代谢的变化将有助于理解碳水化合物限制饮食可能带来的好处，并有助于识别那些更有可能从饮食碳水化合物限制中受益的人，而不是脂肪和卡路里限制（即，量身定制饮食计划的能力，而不是目前的“一六通”方法）。

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 associatd co-morbidities are among the most prevalent and challengin conditions confronting the medical profession in the 21st century. current dietary recommendations from the NIH for weight loss have historically proven difficult to initiate and maintain. Additionally, recommended diets for diabetic patients have proven effective in the short-term but fall short in aiding glycemic control in the long-term. The newly popular carbohydrate-restricted diet may offer benefits to those seeking weight reduction and improved glycemic control greater than those realized with a low-fat, high-carbohydrate, calorie-restricted diet. However, little is known about the effect of either of these diets on hepatic gluose metabolism. This study seeks to determine the impact of severe dietary carbohydrate restriction on hepatic glucose metabolism in terms of the sources of precursors for glucose produced by the liver (glycogen, glycerol, and pyruvate) and the flux of intermediates through the Krebs' cycle, postphoenolpyruvate carboxykinase, and pyruvate recycling. Identifying alterations in hepatic glucose metabolism will aid in the understanding of the benefits a carbohydrate-restricted diet may have and may aid in identification of those persons more likely to benefit from dietary carbohydrate restriction versus fat and calorie restriction (i.e., the ability to tailor a diet plan as opposed to the current one-sixe-fits-all approach).