Diabetes mellitus, a prevalent disease characterized by long-term, devastating medical complications, is a major economic drain on our nation's health care system. Consequently, there is a great need for development of more efficacious drugs for preention and treatment of the disease. The development of combinatorial chemistry technologies has rapidly expanded the repertoire of potential drugs for treatment of diabetes and other diseases. However, this explosion in the creation of new identification of those molecules with therapeutic potential. BetaGene, Inc. seeks to alleviate this rate-limiting step in the discovery and development of compounds that target the pancreatic beta-cell by providing engineered beta- cell lines as novel tools for use in biologically relevant, predictable, high- throughput screens. The feasibility of using engineered cell lines in screens that target the pancreatic beta-cell will be assessed by: (1) determining the stability of secretory function in BetaGene's engineered rodent beta-cell lines through 4 months of continuous culture; (2) determining the capacity of the cells to stably respond to a variety of physiological and pharmaceutical modulators of insulin secretion, and (3) adapting the cells to culture conditions for high throughput screening assays. PROPOSED COMMUNICATION PROPOSAL: Engineered beta-cell lines are likely to expedite discovery and optimization of lead compounds, and thereby provide a means for reducing drug development time and expense. In addition, this technology could be a unique reagent for the development of new classes of compounds for the treatment of NIDDM.