EXTRAHEPATIC GLUCOSE PRODUCTION AND ITS ROLE IN METABOLICDISEASES

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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.