ADIPONECTIN IN PERSONS OF WEST AFRICAN ANCESTRY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 与白色美国人（WA）相比，具有共同遗传的非洲裔美国人（AA）和加纳人（GHA）具有更高的胰岛素抵抗（IR）/高胰岛素血症和更低的肝脏胰岛素提取（HIE）。我们已经表明，IGT和2型糖尿病（T2 DM）的发病机制是相同的AA和GHA，无论地理位置。最近，我们报道了AA谁是胰岛素抵抗和高胰岛素血症与减少缺氧缺血性脑病有较低的脂联素水平。我们推测脂联素（ADIPO）轴失调（adipo基因表达、脂联素蛋白水平、脂联素受体R1（骨骼肌）和R2（肝脏和脂肪组织））可能是黑人和WA中T2 DM患病率差异的部分原因。因此，本研究的具体目的是：AIM#1：研究24小时生理混合餐期间脂联素水平、ADIPO基因和ADIPO受体1和2基因表达与血清葡萄糖、胰岛素和c肽之间的关系AIM#2：研究ADIPO水平、ADIPO基因表达和脂联素受体1和2基因表达与胰岛素分泌急性期和胰岛素敏感性和处置指数之间的关系AIM#3：为了证明生理性高胰岛素血症（10 uU/ml）下调骨骼肌和脂肪组织脂联素基因和脂联素受体基因表达，AIM#4.研究有或无T2 DM家族史的高危AA、GHA移民和WA患者中与急性胰岛素分泌、胰岛素敏感性、DI和肝脏胰岛素敏感性相关的低分子量和高分子量脂联素复合物。

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. African Americans (AA) and Ghanaians (GHA) with a common genetic inheritance have greater insulin resistance(IR)/hyperinsulinemia and decreased hepatic insulin extraction(HIE) when compared with White Americans (WA). We have shown that the pathogenetic mechanisms for IGT and type 2 diabetes (T2DM) are identical in AA and GHA, irrespective of geographic locations. Recently, we have reported that AA who are insulin resistant and hyperinsulinemic with decreased HIE have lower adiponectin levels. We have postulated that adiponectin (ADIPO) axis dysregulation (adipo gene expression ¿Adiponectin protein levels¿adiponectin receptor R1 (skeletal muscle) and R2 (liver and adipose tissue) could partly be responsible for the differences in the prevalence of T2DM in blacks and WA. Thus, our specific aims of the present R01 are:AIM#1:To investigate the relationships between adiponectin levels, ADIPO gene and ADIPO receptors 1 and 2 gene expression and serum glucose, insulin and c-peptide during 24hr physiologic mixed meal ingestions AIM#2:To investigate the relationships of ADIPO levels, ADIPO gene expression and adiponectin receptors 1 and 2 gene expression and acute phases of insulin secretion and insulin sensitivity and disposition index AIM#3:To demonstrate that physiologic hyperinsulinemia (10uU/ml) down regulates skeletal muscle and adipose tissue adiponectin gene and adiponectin receptor gene expression AIM#4.To examine the molecular species i.e. low and high molecular weight adiponectin complexes that are associated with acute insulin secretion and insulin sensitivity and DI and hepatic insulin sensitivity in high risk AA, GHA immigrants and WA with and without family history of T2DM.