Grant: Project Grant

In the pancreas, alpha-cells release glucagon (which causes blood sugar to go up) and beta-cells release insulin (which causes blood sugar to go down). In type-1 diabetes, beta-cells are destroyed by inflammation. Glucagon release however also does not work properly, which can cause life-threatening low blood sugar after insulin injections. No treatment has been developed to regulate glucagon secretion. Dr. Herbert Gaisano is examining pancreatic alpha-cells to: 1) determine how glucagon is normally released which is surprisingly unclear, 2) why glucagon is not released properly in type-1 diabetes, and then 3) determine if there are ways to fix this process. To do this, his laboratory has devised unprecedented imaging technologies to visualize alpha-cell glucagon secretion as dispersed single cells, and also alpha-cells within the intact pancreas in health and in type-1 diabetes. In diabetes, alpha-cells are profoundly influenced by lack of secretion from neighboring beta-cells (destroyed) and excess secretion from delta-cells (somatostatin that inhibits alpha- and beta-cells). Knowing precisely how neighboring islet cells normally communicate with each other, and become unneighbourly to alpha-cells in diabetes will reveal new paradigms in treating diabetes.