This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 2 diabetes is recognized as a major health problem in the African-American community, and the incidence of type 2 diabetes has been increased relative to other US populations. The underlying cause is hyperinsulinemia associated with increased insulin resistance, and the propensity to this phenotype is already seen in African-American children relative to white American peers. As muscle is the primary insulin uptake organ in the body and there is well-documented association of insulin uptake and exercise, we hypothesized that exercise might induce a series of insulin metabolic pathways, some of which might act systemically. The purpose of this protocol is to conduct a complete single nucleotide polymorphisms (SNPs) discovery study in five candidate genes that are involved in insulin regulation and modulated by exercise as well as other genes that are found to be associated with glucose metabolism. The identified SNPs will then be genotyped in African-American children with type 2 diabetes, and age-and gender-matched obese, African-American children without type 2 diabetes. We will screen 50 randomly ascertained African-Americans and Hispanics for SNPs in CTAP III, alpha-endosulfine, IGF-1 receptor, PEA-15, and TIC/BMal1b as well as other genes associated with glucose metabolism, and identify common haplotypes in the African-American and Hispanic populations. Then, we will use representative SNPs to genotype for haplotypes in a series of 60 African-American and Hispanic children with type 2 diabetes or predisposed towards type 2 diabetes (based on obesity and/or impaired glucose tolerance) and 60 age- and gender-matched African-American and Hispanic children without type 2 diabetes. We will conduct a pilot association study to determine if any haplotype shows an association with type 2 diabetes or predisposition to type 2 diabetes in African-American and/or Hispanic children.
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