EXTRAHEPATIC GLUCOSE PRODUCTION AND ITS ROLE IN METABOLICDISEASES

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，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。这是一个新的合作项目，现在由美国糖尿病协会青年教师奖（ADA 1-05-JF-05）支持。虽然人们普遍认为非肝组织可以促进葡萄糖的产生，但这种情况发生的程度和代谢条件尚不清楚。非肝脏来源的葡萄糖可能对糖尿病的病理生理学和可能的治疗靶点很重要。研究肝外新生血管的困难之一是缺乏良好的动物模型。第二个问题是缺乏可用于研究肝外血管生成的方案。我们一直在研究肝特异性PEPCK敲除（KO）小鼠作为肝外肝再生的模型，最近发现其内源性葡萄糖产生的60%来自非肝脏来源。目前正在开发以稳定同位素示踪剂和NMR光谱为中心的体内和离体方法，并将其应用于包括PEPCK KO小鼠以及其他糖尿病动物模型在内的系统。这些努力将产生关于肝外葡萄糖产生在代谢性疾病中的作用的新信息。如果没有UTSWMC研究资源的支持，这项工作是不可能完成的。

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. This is a new collaborative project, now supported by an American Diabetes Association Junior Faculty Award (ADA 1-05-JF-05). Although it is commonly accepted that non-hepatic tissue can contribute to glucose production, the extent and metabolic conditions in which this takes place is unknown. Non-hepatic sources of glucose may be important to the pathophysiology of diabetes and possible targets for therapy. One difficulty in studying extra-hepatic gluconeogenesis is the lack of a good animal model of the phenomenon. A second problem is a deficiency of protocols that can be used to study extra-hepatic gluconeogenesis. We've been studying the hepatic specific PEPCK knockout (KO) mouse as a model of extra-hepatic gluconeogenesis and have recently shown that 60% of its endogenous glucose production comes from non-hepatic sources. In vivo and ex vivo approaches centered around stable isotope tracers and NMR spectroscopy are being developed and applied to systems including the PEPCK KO mouse as well as other animal models of diabetes. These efforts will yield new information about the role of extra-hepatic glucose production in metabolic diseases. This work would be impossible to accomplish without the support of the Research Resource at UTSWMC.