Phenotypes and genes linked toinsuline resistance and risk for type 2 diabetes (CAUSE OF TYPE 2 DIABETES)

Type 2 diabetes is a major global health problem which is undergoing an epidemic development. Effective intervention and treatment require the understanding of the genetic and molecular mechanisms involved. The objectives of this proposal are to identify at least 800 healthy first-degree relatives to Type 2 diabetic subjects. and a similar control group lacking known genetic predisposition. Extensive and novel technology will be used to characterize clinical subphenotypes. Adipose and muscle biopsies will be obtained for analyses of gene expression using the novel cDNA array technology. Differentially expressed cDNAs will be identified and cloned and biological functions of novel proteins identified. Transgenic/knock-out animals will be generated to identify in vivo functions. In parallel, focused research will be performed aimed at identifying candidate genes, including intracellular signaling molecules and nuclear receptor transcription factors.