EXCESS GLUCOSE PRODUCTION: GLYCOGEN OR TCA-CYCLE GLUCONEOGENESIS?

葡萄糖产生过多：糖原或 TCA 循环糖异生？

• 批准号: 7357902
• 负责人: EUNSOOK JIN
• 金额: $ 2.35万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7357902
• 关键词: Krebs' cycle; fasting; gluconeogenesis; glucose; glycogen; glycogenolysis; hyperglycemia; liver; role

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. A male Zucker diabetic fatty (fa/fa) rat is a genetically modified rodent model with nonfunctional leptin receptors for type 2 diabetes mellitus (T2DM) associated obesity. Early studies of glucose metabolism in fa/fa rats have focused on resistance to liver glycogen depletion in fasted condition. Substantial liver glycogen store in fasted fa/fa rats could be a significant contribution for fasted hyperglycemia because glucose production (GP) and relative glycogenolysis/gluconeogenesis are under the influence of liver glycogen storage. Glucose over-production has a major role in fasted hyperglycemia of T2DM, but the relative roles of glycogenolysis and gluconeogenesis remained controversial. Another factor in over-production of glucose may be excess TCA cycle flux driven by excess plasma FFA. The objectives of this study are (i) to compare comprehensive GP patterns of prediabetic and overt diabetic stages of fa/fa rats, and (ii) to evaluate the role of hepatic glycogen in hyperglycemia of fasted conscious fa/fa rats.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。列出的机构适用于该中心，这不一定是调查员的机构。雄性扎克糖尿病脂肪（FA/FA）大鼠是一种基因修饰的啮齿动物模型，具有非功能性瘦素受体，用于2型糖尿病（T2DM）相关的肥胖症。 FA/FA大鼠葡萄糖代谢的早期研究已集中在禁食状态下对肝糖原消耗的抗性。禁食的FA/FA大鼠中的大量肝糖原储存可能是禁食性高血糖的重要贡献，因为葡萄糖产生（GP）和相对糖基溶解/糖异生在肝糖原储存的影响下。葡萄糖过量产生在禁食的T2DM高血糖中具有重要作用，但是糖原分解和糖异生的相对作用仍然存在争议。葡萄糖过度生产的另一个因素可能是过量血浆FFA驱动的过量TCA循环通量。这项研究的目标是（i）比较FA/FA大鼠的糖尿病前期和公开糖尿病阶段的全面GP模式，以及（ii）评估肝糖原在禁食有意识的FA/FA大鼠高血糖中的作用。