SBIR-STTR Award

Impaired insulin-regulated glucose clearance by skeletal muscle is an early event in the development of noninsulin dependent diabetes mellitus (NIDDM), a potentially lethal condition, which affects over S million people at estimated costs of ova $20 billion annually in the US alone. Several lines of evidence indicate that reduced expression of hexokinase II (HKII) activity may be responsible for this. Our goal is to identity novel orally-administered therapeutic agents to stimulate the expression of the HKII gene in order to better control blood glucose levels in NIDDM. To facilitate drug discovery, we will develop an automated high-throughput cell-based drug screen using skeletal muscle cells stably transfected with a luciferase reporter vector controlled by the deregulatory elements of the HKII gene. This approach permits rapid evaluation of large natural product libraries or collections of compounds, making it possible to consider leads representing as much molecular diversity as possible. In Phase I we will prepare the reporter cell line, and in preparation for lead follow-up studies, will investigate a novel cell culture system for studying the regulation of glucose uptake in skeletal muscle. The drug screen and follow-up studies will be performed in Phase II.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

There is no text on file for this abstract.Thesaurus termsdrug screening /evaluation, hexokinase, hypoglycemic agent, noninsulin dependent diabetes mellitus, transcription factor enzyme induction /repression, gene expression, glucose metabolism, glucose transporter, muscle cell cell line, disease model, laboratory mouse, oral administration, polymerase chain reaction, reporter gene, transfection vector, western blottingNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)