DEVELOPMENT OF NOVEL THERAPIES FOR NIDDM

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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. Recombinant adenoviruses are a tool for delivery of genes that can modulate the balance between hepatic glucose disposal and production in animal models of diabetes, thereby gaining insights into mechanisms of hepatic dysfunction in the disease as well as novel therapeutic strategies. In recent years this work has focused on a family of glycogen targeting subunits of protein phosphatase-1 (PP-1). The proteins serve as scaffolds for juxtaposing PP-1 with its substrates glycogen phosphorylase, glycogen synthase, and phosphorylase kinase. Early collaborative studies with the Rogers Center used 13C NMR to demonstrate that adenovirus-mediated expression of PTG, a targeting subunit family member, stimulates glycogen synthesis by the indirect (gluconeogenic) pathway.