Preventing Islet Death and Dysfunction With Viral Proteins
Dr. Patrick MacDonald
In diabetes the insulin producing cells within pancreatic islets of Langerhans are either destroyed through an autoimmune reaction (type 1 diabetes) or are dysfunctional and are ultimately lost (type 2 diabetes). In islet transplantation also, there is both an immediate and long term loss of function and islet mass that results in the patient returning to insulin injections. In all of these cases, inflammation leading to cell death is thought to play an important role, and preventing inflammation or inflammatory signals is thought to be beneficial in diabetes. Clinical evidence using anti-inflammatory agents supports this.
Viruses survive and proliferate by invading and taking over host cells in order to replicate. Most viruses have found ingenious ways to keep host cells alive long enough to allow viral replication. To do this, viruses produce a number of proteins that block both extracellular inflammation and intracellular cell death pathways.
In the present work we will take advantage of these novel pro-survival proteins made by viruses to protect pancreatic islets from the dysfunction and death caused by inflammation and high glucose. We will perform proof-of-concept studies to evaluate the ability of several virus-derived proteins to prevent both the dysfunction (calcium signals and insulin secretion) and death of isolated mouse and human islets in culture. This work will lead to further pre-clinical studies of protective proteins in animals, and we hope to eventual clinical trials in the areas of type 1 and type 2 diabetes, and in islet transplantation.