Type 2 Diabetes is at epidemic proportions today. Changes in energy utilization, myocardial remodeling and left ventricular hypertrophy are early manifestations of diabeteic cardiomyopathy. Eventually the heart succumbs to this debilitating disease making heart failure the number one form of death from diabetes. Front line therapy for type 2 diabetes is the class of nuclear receptor agonists, thiazolinedoines (TZDs), which are used for improving insulin sensitivity and glucose handling. My research focuses upon the mechanism by which the class of nuclear receptors (PPAR-gamma, PPAR-delta and PPAR-alpha) affects heart function and physiology under diabetogenic dietary insult, a model for type 2 diabetes and metabolic syndrome X.
My current research utilizes transgenic animals, and primary heart cells to better understand the mechanism by which activation of these nuclear receptors controls the promoter activity of specific gene targets which are involved in regulating myocardial energy homeostasis such as fatty acid metabolism and glucose modulation. This goal will be accomplished by using chromatin immuno-precipitation and promoter activity assays; more specifically these techniques will better elucidate the role in which the nuclear receptors and transcriptional co-regulators control endogenous adiponectin expression and energy metabolism in the heart. The goal will then allow a better understanding as to how this protein and nuclear receptors protects the heart against diabetogenic stress and myocardial remodeling.
Amin, R., Mathews, S., Alli, A., & Leff, T. (2008) Endogenous Production of Adiponectin in Heart Contributes to the Cardioprotective Effect of PPAR-Gamma. Submitted for publication.
Yang, H., Youm, Y-H., Nakata, C., Floyd, E., 3, Smith S. R., Amin, R., Leff, T., and Dixit, V. (2008) PPAR Gama regulates thymic involution via adipocyte accretion within thymus. Submitted for publication
Amin, R., Mathews, S., Camp, H.S., Ding, L., & Leff, T. (2008). Selective expression of constitutive-active PPAR-Gamma in skeletal muscle improves insulin sensitivity. Submitted for publication
Varanasi U. Amin RH and Leff T. Chromatin Associated AMPK alpha-2 May Regulate Nuclear Receptor HNF4 (2008) Manuscript in prep.