HEPATIC MITOCHONDRIAL METABOLISM DURING INSULIN RESISTANCE

胰岛素抵抗期间的肝脏线粒体代谢

• 批准号: 7956952
• 负责人: SHAWN M BURGESS
• 金额: $ 1.78万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956952
• 关键词: Binding Proteins; Biochemical; Carbohydrates; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Diet; Enzyme Gene; Enzymes; Fatty acid glycerol esters; Funding; Genes; Genetic Transcription; Glycolysis; Grant; Hepatic; Institution; Insulin; Insulin Resistance; Intake; Liver; Metabolism; Mitochondria; Mus; Organ; Oxidation-Reduction; Pancreas; Pyruvate; Pyruvates; Research; Research Personnel; Resources; Response Elements; Signal Transduction; Source; Starch; United States National Institutes of Health; feeding; in vivo; lipid biosynthesis; response; transcription factor

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. When carbohydrate intake exceeds short-term requirements for energy, it is stored as fat. The liver is the principle organ responsible for the conversion of excess carbohydrate to fat. Ingesting a high carbohydrate diet induces gene transcription of over a dozen enzymes in liver that are involved in glycolysis and fat synthesis. Insulin, secreted by the pancreas in response to carbohydrate promotes lipogenesis by activating lipogenic enzyme expression. However, carbohydrates also stimulate transcription of the same genes independent of insulin. The mechanism by which metabolizable carbohydrate generates a signal to induce the transcription of lipogenic enzyme genes became clearer with discovery of the transcription factor termed carbohydrate response element binding protein (ChREBP). The purpose of this collaboration is (a) to determine the biochemical mechanism for the reduced REDOX state of liver of ChREBP-/-, and (b) to determine the source of pyruvate in the liver of ChREBP-/- mice fed high starch diet.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 当碳水化合物的摄入量超过短期能量需求时，它会以脂肪的形式储存起来。 肝脏是负责将多余的碳水化合物转化为脂肪的主要器官。 摄入高碳水化合物的饮食会诱导肝脏中参与糖酵解和脂肪合成的十几种酶的基因转录。 胰腺分泌的胰岛素对碳水化合物有反应，通过激活脂肪生成酶的表达促进脂肪生成。 然而，碳水化合物也刺激不依赖胰岛素的相同基因的转录。 随着被称为碳水化合物反应元件结合蛋白（ChREBP）的转录因子的发现，代谢性碳水化合物产生信号以诱导脂肪生成酶基因转录的机制变得更加清楚。 这项合作的目的是（a）确定ChREBP-/-肝脏REDOX状态降低的生化机制，以及（B）确定喂食高淀粉饮食的ChREBP-/-小鼠肝脏中丙酮酸的来源。