Assays for insulin and insulin-like regulation of gene and protein expression.

Part of the blood glucose-lowering activity of insulin is based on massive and specific up- or downregulation of the gene expression for proteins/enzymes which directly regulate carbohydrate and lipid metabolism (e.g., GLUT4, PEPCK). Furthermore, changes in the intermediary metabolism provoked by insulin may secondarily lead to alterations in the gene/protein expression of other signaling/metabolic pathways. Consequently, it is important for the identification as well as characterization of compounds/drug candidates with insulin-like activity to analyze their effect on the expression of gene and proteins. For practical reasons, this analysis can be restricted to those genes/proteins which according to the present knowledge are relevant for mode of action of the compound/drug candidate. However, undoubtedly whole genome or proteome searches for changes in the expression levels have important advantages, in particular due to its unbiased nature. However, they require considerable experimental expenditure and time on basis of conventional technology. This may change completely with the successful introduction of protein chips and DNA microarrays for the study of protein and gene expression and further increase its attractiveness for routine application in characterization of novel compounds/drug candidates