An Autoantibody In Type 1 Diabetes That Mediates Autonomic Complications
Funder
National Health and Medical Research Council
Funding Amount
$254,591.00
Summary
Type 1 diabetes is a chronic autoimmune disease characterised by destruction of insulin producing cells in the pancreas. One of the most common and serious complications of type 1 diabetes is disruption of the autoimmune nervous system, and once symptoms appear the 5-year mortalityrate is approximately 50%. Symptoms of autonomic dysfunction can be extensive, and involve the stomach, intestine, bladder, heart and reproductive organs. Currently, the management of autonomic dysfunction remains prim ....Type 1 diabetes is a chronic autoimmune disease characterised by destruction of insulin producing cells in the pancreas. One of the most common and serious complications of type 1 diabetes is disruption of the autoimmune nervous system, and once symptoms appear the 5-year mortalityrate is approximately 50%. Symptoms of autonomic dysfunction can be extensive, and involve the stomach, intestine, bladder, heart and reproductive organs. Currently, the management of autonomic dysfunction remains primative due to our poor understanding of the mechanisms underlaying the disease. Recent work from our group has identified an excitatory autoantibody (an antibody against the self) to calcium channels in patients with type 1 diabetes. The anti-calcium channel autoantibody profoundly disrupts gut and bladder function by interfering with autonomic regulation of smooth muscle within these organs. The anti-calcium channel autoantibody is the first functional autoantibody to be detected in type 1 diabetes, and represents a conceptual advance in our understanding of immune mechanisms in this disease. Using animal models and a panel of novel, functional assays of colon, stomach and bladder we will investigate how the anti-calcium channel autoantibodies contribute to autonomic dysfunction in type 1 diabetes. Understanding the mechanisms by which this autoantibody effects autonomic regulation of organ function will enable the development of new therapeutic strategies for better management of patients.Read moreRead less
The Role Of Interleukin-21 In The Pathogenesis Of Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$519,000.00
Summary
T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that th ....T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that the pancreas can no longer make insulin. Diabetes is a life-threatening disease because insulin is a hormone that enables people to get energy from food. Type 1 diabetes is usually diagnosed in childhood and insulin must be administered daily by injection or through a pump in order to survive. Unfortunately, taking insulin doesn t cure diabetes and people continue to suffer from an extensive list of complications affecting most vital organs. Interleukin-21 (IL-21) is a soluble protein that is produced by cells enabling them to communicate with other cells. IL-21 helps cells to produce factors that cause inflammation and assist in clearance of viruses and bacteria from the body. However, our studies show that IL-21 is a major factor in the development of the T cells that destroy beta cells and cause diabetes. Our studies show that IL-21 is over-expressed in an important murine model of spontaneous type-1 diabetes. We have isolated the T cells that cause diabetes and show that they are distinguished from other T cells by very high levels of the receptor for IL-21. This project focuses on the IL-21-responsive T cells that cause diabetes and aims to determine the mechanisms by which the cytokine IL-21 causes destructive immune responses and ways to modulate its production. This project applies basic science to the important public health issue of type 1 diabetes for the development of therapeutic intervention strategies.Read moreRead less