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Leissring, Malcolm Arthur
Role of insulin-degrading enzyme in the pathogenesis and potential treatment of diabetes

General Research Subject: Type 2 Diabetes
Focus: Insulin Action\Insulin Resistance, Insulin Action\Metabolism, Insulin Action\Signal Transduction
Type of Grant: Career Development
Project Start Date: July 1, 2011
Project End Date: June 30, 2016
Research Description
Insulin is a key hormone the helps lower sugar levels in the blood, a function that is disrupted in diabetes. This study will test whether inhibiting the breakdown of insulin in the body can help insulin work longer and more effectvely, a key goal in the treatment of diabetes. Insulin is broken down by an enzyme called insulin-degrading enzyme, and this study will investigate whether reduced levels of this enzyme in mice can help insulin more efficiently lower blood sugar levels. This study will also test candidate drugs that inhibit this enzyme to determine whether such drugs might be useful for treating diabetes.
Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project is focused on insulin metabolism, specifically the breakdown of insulin by insulin-degrading enzyme (IDE). We hypothesize that inhibiting IDE partially will boost insulin levels by slowing its metabolism. This is a fundamentally different approach to treating diabetes that could lead to novel treatments.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
One day, you may be able to take a pill that makes your insulin work better, by slowing the breakdown of insulin in the body.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I have been studying insulin-degrading enzyme for more than 10 years. Surprisingly, we know more about IDE's role in Alzheimer's thanwe do in diabetes, even though IDE is known to be the major enzyme responsible for breaking down insulin. I have always been interested in how IDE relates to diabetes. This award provides the seed money to begin to study this fascinating topic.
In what direction do you see the future of diabetes research going?
There is a big need for improved delivery of insulin as well as for
drugs that help regulate blood sugar, and IDE plays a key role in both.
The IDE inhibitors we are developing and testing will potentially be a
part of a new generation of antidiabetic therapies.
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