TCD Scientists Make Significant Type 2 Diabetes Breakthrough
Posted on: 13 September 2010
Scientists at Trinity College Dublin have discovered what could be the underlying basis for Type 2 diabetes, a debilitating disease where people stop responding to insulin. The TCD team has found that the peptide hormone, Islet Amyloid Polypeptide (IAPP), which gets deposited in the pancreas in Type 2 diabetes, is the trigger for a protein complex called the inflammasome. This in turn leads to the production of the pro-inflammatory agent IL-1beta, which is already being targeted in several clinical trials. The study carried out in the Science Foundation Ireland-funded Immunology Research Centre is published this week in the world’s leading immunology journal, Nature Immunology.
“We’ve found what might be the ‘straw that breaks the camel’s back’ in Type 2 diabetes,” says Dr Seth Masters, lead author on the publication. “IL-1beta is known to be important in the disease and we have found what might be the key mechanism leading to its over-production.”
Type 2 diabetes is a disease whose incidence is increasing in Ireland and in the Western world in general because of increasing obesity. The work provides a deeper insight into the disease process.
In the Republic of Ireland alone it is estimated that up to 14% of the population over 40 years of age has diabetes and that 10% of our healthcare budget is spent treating diabetes and its complications. Every year 4 million people globally, and over 2,000 people in Ireland die from diabetes-related diseases. It is associated with obesity and there is a major need to provide better treatments. Symptoms can include fatigue, blurred vision, failure to heal wounds and damage to organs including the eyes and kidneys. Type 2 diabetics have a higher risk of suffering a heart attack, the same as those who have previously had a heart attack.
“Current treatments are somewhat effective but there is a pressing need for newer therapeutic approaches,” says Professor of Biochemistry, Luke O’Neill, who heads the group at TCD. “IL-1beta is being explored by several drug companies and results are promising. Our work confirms the importance of IL-1beta in the disease and also points to Nlrp3 as a new target to go after.”
Opsona Therapeutics, co-founded by Luke O’Neill, has an active programme in this area. The work is likely to spur further efforts to develop drugs that interfere with this process. “Mechanistic insights such as the one we have made are very important for the effort to develop new therapies. There is real optimism that much better treatments for Type 2 diabetes will emerge from this area,” says Prof O’Neill.
The work involved collaborators in UCD, and the Universities of Washington, Michigan and Kyoto.
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