ADIPONECTIN IN PERSONS OF WEST AFRICAN ANCESTRY

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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.