My research focuses on cellular mechanisms underlying islet secretory dysfunction and loss of beta-cell mass in diabetes. Our interest lies not only in beta-cell intrinsic mechanisms of failure, but also how other cell types in the islet modulate beta cell function and dysfunction. We are currently investigating the role of the islet endothelial cell in determining islet function, and studying the composition of the islet extracellular matrix under conditions of health and disease. Our studies utilize a variety of physiology, cell biology and histochemical approaches.
My laboratory studies mechanisms underlying islet dysfunction in models of type 2 diabetes. This research falls into three main areas:
Islet endothelial dysfunction. The islet has an extensive capillary network, comprising endothelial cells and other supporting cell types. We hypothesize that endothelial dysfunction affects the islet, as occurs in other vascular beds in diabetes, and that this may contribute to islet secretory dysfunction in diabetes. We use several animal and cell-based models to investigate this question.
Extracellular matrix in the islet. Normal islet function, and thus glucose homeostasis, requires communication among the many cell types that comprise the islet. The extracellular matrix is a key regulator of cell-cell signaling. Ongoing projects in this area include identification of novel islet extracellular matrix components and how these are dysregulated in models of diabetes.
Islet amyloid deposition. Islet amyloid deposits occur in the vast majority of individuals with type 2 diabetes and the extent of amyloid deposition is associated with decreased beta cell mass in humans and animal models. This has been a focus of my research for many years. Ongoing studies include understanding the role of heparan sulfate proteoglycans in islet amyloid formation.
