Regulation of Insulin Secretion by PI3 Kinase
Dr. Patrick MacDonald
Our main interests lie in understanding the mechanisms that control hormone release from the endocrine pancreatic islets of Langerhans, and how this is disrupted in diabetes. We study the control of both insulin and glucagon secretion, with a particular interest in elucidating the metabolic and receptor-mediated signaling mechanisms that control key ion channels and exocytotic processes responsible for secretion. We have a major interest in asking these questions, not only in standard experimental models such as cell lines and rodent islets, but also in pancreatic islets isolated from human donors. As such, we run a human research islet program, aimed at understanding the mechanisms that control human insulin (and glucagon) secretion in health and disease. Current projects include studies of the voltage-dependent K+ channel (Kv2.1) as a regulator of insulin and glucagon release; the regulation of insulin granule dynamics by PI3 kinases in an isoform-specific manner; the role of post-translational SUMOylation in insulin exocytosis and ion channel function; and interactions between metabolic stress and inflammatory cytokines in islet secretory dysfunction and apoptosis.