Our lab studies Diabetes mellitus (DM), the most prevalent human metabolic disease; it results from loss and/or dysfunction of b-cells in pancreatic islets. Accumulating evidence suggests that ß-cell apoptosis contributes to the pathophysiology in both types 1 and 2 diabetes mellitus. We identified the participation of a Ca2+-independent phospholipase A2 in ß-cell apoptosis and the goals of this project are to understand the mechanism by which lipid mediators contribute to ß-cell death. Recent studies suggest an interplay between pancreatic islets and osteoblasts and our goal is to elucidate the signaling pathways that link these two “endocrine” organs. Bioactive arachidonic acid (AA) metabolites (eicosanoids) generated by the actions of 5-lipoxygenase (5-LO) and cyclooxygenase (COX) are important mediators of bone remodeling. The introduction of PIs in 1995 has resulted in marked decreases in mortality among HIV+ patients from 30% achieved with RTs combination therapy alone to 8% with the addition of a PI. However, inclusion of PIs in the therapeutic regimen is also associated with peripheral lipoatrophy, visceral adiposity, hyperlipidemia, insulin resistance, hyperglycemia, and overt type 2 diabetes mellitus. Our studies indicate the involvement of a novel signaling cascade in PI-Induced insulin resistance and diabetes and the goals of this project are to describe the mechanism(s) by which chronic PI treatments induce metabolic abnormalities.
