We study the role of lipid dynamics in regulating membrane composition and trafficking in the secretory and endocytic pathways. Our primary focus is on the cellular mechanisms that distribute cholesterol to support the storage and secretion of insulin by endocrine pancreatic beta cells. Cholesterol is concentrated in the membranes that surround packaged insulin, and its levels are maintained within narrow limits to insure both stable intracellular storage and optimal glucose-stimulated secretion. Moreover, beta cells control the amount of stored insulin by coordinating the rates of proinsulin biosynthesis, insulin release and granule turnover by degradation. We are interested whether granule cholesterol level is a key determinant in maintaining cellular insulin homeostasis. To explore these issues, we use a variety of molecular, biochemical, and microscopic imaging approaches to analyze how manipulation of cholesterol regulatory machinery affects insulin granule formation, storage, release and turnover. We examine these events in insulin-producing cell lines and primary cultures of pancreatic islet cells.
Image: Cholesterol regulatory protein OSBP concentrated at sites of insulin granule formation.
Research interests field: Intracellular cholesterol and the regulation of insulin secretion and membrane trafficking.