Our laboratory is interested in the endocrine mechanisms associated with diabetes mellitus and its complications. Diabetes or insulin insufficiency is characterized by changes in nutrient metabolism as well as chronic alterations in multiple physiological systems. Cardiovascular changes and hypertension are characteristic of diabetes and are the basis for the major complications of diabetes such as increased risk of heart attack, vascular dysfunction, and stroke. Since obesity is strongly associated with diabetes we are also investigating the role of insulin and adipose tissue hormones in the central nervous system (CNS)-mediated regulation of cardiovascular responses. We are investigating the hypothalamic factors mediating the leptin signaling cascade pathway. We have evaluated the interaction of the proopiomelanocortin system (POMC) and its major products aMSH and beta-endorphin and their receptors in this process. We are conducting studies on the mechanism of action of insulin and leptin in the regulation of blood flow dynamics. We are also conducting studies to evaluate the peripheral actions of these hormones contrasted to their actions mediated at the level of the central nervous system (CNS).