TYPE 2 DIABETES IN AFRICAN-AMERICAN CHILDREN: EXERCISE/INSULIN-RELATED MUSCLE SN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在非裔美国人社区中，2型糖尿病被认为是一个主要的健康问题，相对于其他美国人群，2型糖尿病的发病率有所增加。潜在的原因是与胰岛素抵抗增加相关的高胰岛素血症，相对于美国白人同龄人，这种表型的倾向已经在非裔美国儿童中看到。由于肌肉是人体主要的胰岛素摄取器官，而且胰岛素摄取与运动之间存在着良好的联系，我们推测运动可能会诱导一系列的胰岛素代谢途径，其中一些可能是系统性的。该方案的目的是在5个参与胰岛素调节和运动调节的候选基因以及其他与糖代谢相关的基因中进行完整的单核苷酸多态(SNPs)发现研究。然后，将对患有2型糖尿病的非裔美国儿童以及年龄和性别匹配的肥胖、没有2型糖尿病的非裔美国儿童进行SNPs基因分型。 我们将对50名随机确定的非洲裔美国人和西班牙裔美国人进行CTAP III、α-内磺胺、IGF-1受体、PEA-15和TIC/BMal1b以及其他与糖代谢相关的基因的SNPs筛查，并确定非洲裔和西班牙裔群体中常见的单倍型。然后，我们将使用具有代表性的SNPs对60名患有2型糖尿病或易患2型糖尿病(基于肥胖和/或糖耐量受损)的非裔美国人和西班牙裔儿童以及60名年龄和性别匹配的非裔美国人和西班牙裔非2型糖尿病儿童进行单倍型分型。我们将进行一项试点关联研究，以确定是否有单倍型与非裔美国人和/或西班牙裔儿童的2型糖尿病或2型糖尿病易感性有关。

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.