New Agents That Keep Insulin Working Longer

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Scientists at the Mayo Clinic have developed a molecule that can block the breakdown of insulin. Their discovery could lead to development of a new class of drugs to help treat diabetes.

"The discovery may lead to drugs that diabetics can use to help insulin work better and longer", says the study's lead researcher, Malcolm Leissring, Ph.D., in a press release from the Mayo Clinic's Department of Neuroscience.

By inhibiting an insulin-degrading enzyme (IDE) from destroying insulin, the new molecule allows insulin to stay in the circulation longer. Usually, the liver destroys about half of the insulin produced by the pancreas. The IDE inhibitors would not only slow this destruction by the liver, according to the study, but also help prevent the destruction of insulin when it is in the bloodstream working to facilitate the absorption of glucose into the cells of the body.

"When insulin reaches cells, it is normally destroyed very rapidly by IDE. We show that when you stop that process with an IDE inhibitor, insulin stays around longer inside the cell, allowing the hormone to function more efficiently," Dr Leissring says.

IDE was discovered more than 60 years ago. An IDE inhibitor was a major goal of diabetes research in the 1950s, with one group of early researchers discovering a naturally occurring IDE inhibitor. They found that the inhibitor made insulin more effective at lowering blood glucose in animals. The composition of the inhibitor, however, was never determined.

Using a special lab technique that helps to determine the shape of molecules, Leissring and colleagues saw that the structure of IDE is unlike other proteases that degrade hormones. It is shaped like a hinged clamshell that opens and shuts. The researchers found from their crystal structure research that their new IDE inhibiting peptide acts like a latch that holds the clamshell shut.

"Insulin is involved in a surprisingly wide range of important processes, including memory and cognition, so IDE inhibitors may turn out to have multiple uses. They also will be very valuable as tools for basic research."

The findings are published in the May issue of PLoS ONE (www.plosone.org), and could create a new avenue for the development of drugs for treating diabetes.