Abstract:

Using live-cell high-resolution imaging of the islets in situ within thin slices of human pancreas, we have been able to reveal new insights into three areas of diabetes islet biology. First, we elucidated the role of inhibitory SNARE proteins (Syntaxin-2) in regulating the pancreatic islet beta-cell exocytotic machinery, which when negated can improve biphasic insulin secretion in type-2 diabetes. Second, we have begun to assess the dynamic spatio-temporal relationships of immune T-lymphocytes (helper CD4 and killer CD8) recruitment to islets, and the initiation of beta-cell injury. Third, people with Cystic Fibrosis (pwCF) are now surviving into their 50’s wherein the major complication is islet dysfunction causing diabetes (i.e. CF-related diabetes or CFRD). We have elucidated new paradigms into CF/CFRD whereby abnormal secretomes released by CFTR-defective pancreatic duct epithelial cells directly induce paracrine beta-cell dysfunction and promote fibrosis in the exocrine and islet compartments, the latter also contributing to islet dysfunction.

Biography:

Herbert Gaisano is an academic gastroenterologist, and a Professor of Medicine and Physiology at the University of Toronto. Dr. Gaisano is a multi-awarded and leading scientist in endocrine and exocrine pancreas. His research focus has been on a class of proteins called SNARE proteins, which he had demonstrated to orchestrate exocytosis and ion channel gating in two secretory cell models - pancreatic acinar cell and islet beta cell. Here, Dr. Gaisano has made pioneering observations that SNARE proteins not only directly mediate exocytotic fusion of secretory granules with the plasma membrane, but also directly bind and regulate calcium and potassium channel gating to fine tune the secretory process; and how these secretory processes could be dysregulated to cause deficient insulin secretion in type-2 diabetes, and pathologic exocytosis leading to pancreatitis. Dr. Gaisano has translated this fundamental biology of SNARE protein regulation of ion channels to non-secretory cells, including gastrointestinal smooth muscle and cardiac myocytes to regulate muscle contractility in health and disease. Dr. Gaisano has pioneered the use of thin slices of the human pancreas in culture to further insights into both exocrine and islet biology, and in current pursuit of two new areas: 1) type-1 diabetes in visualization of T-cell recruitment to and initiation of beta-cell injury, and 2) cystic fibrosis (CF) and CF-related diabetes/islet dysfunction.