Hexokinase II Transcription Activators as Antidiabetics

Impaired insulin-regulated glucose clearance by skeletal muscle is an early event in the developmendependent diabetes mellitus (NIDDM), a potentially lethal condition, which affects over 5 million peof over $20 billion annually in the US alone. Several lines of evidence indicate that reduced expres(HKII) activity may be responsible for this. Our goal is to identity novel orally-administered therathe expression of the HKII gene in order to better control blood glucose levels in NIDDM. To facilitwill develop an automated high-throughput cell-based drug screen using skeletal muscle cells stablyluciferase reporter vector controlled by the 5'-regulatory elements of the HKII gene. This approachof large natural product libraries or collections of compounds, making it possible to consider leadsmolecular diversity as possible. In Phase I we will prepare the reporter cell line, and in preparatistudies, will investigate a novel cell culture system for studying the regulation of glucose uptakedrug screen and follow-up studies will be performed in Phase II.