DGAP (tool)

RRID:SCR_003036

Produce resources to unravel the interface between insulin action, insulin resistance and the genetics of type 2 diabetes including an annotated public database, standardized protocols for gene expression and proteomic analysis, and ultimately diabetes-specific and insulin action-specific DNA chips for investigators in the field. The project aims to identify the sets of the genes involved in insulin action and the predisposition to type 2 diabetes, as well as the secondary changes in gene expression that occur in response to the metabolic abnormalities present in diabetes. There are five major and one pilot project involving human and rodent tissues that are designed to: * Create a database of the genes expressed in insulin-responsive tissues, as well as accessible tissues, that are regulated by insulin, insulin resistance and diabetes. * Assess levels and patterns of gene expression in each tissue before and after insulin stimulation in normal and genetically-modified rodents; normal, insulin resistant and diabetic humans, and in cultured and freshly isolated cell models. * Correlate the level and patterns of expression at the mRNA and/or protein level with the genetic and metabolic phenotype of the animal or cell. * Generate genomic sequence from a panel of humans with type 2 diabetes focusing on the genes most highly regulated by insulin and diabetes to determine the range of sequence and expression variation in these genes and the proteins they encode, which might affect the risk of diabetes or insulin resistance. The DGAP project will define: * the normal anatomy of gene expression, i.e. basal levels of expression and response to insulin. * the morbid anatomy of gene expression, i.e., the impact of diabetes on expression patterns and the insulin response. * the extent to which genetic variability might contribute to the alterations in expression or to diabetes itself.