Compound that blocks insulin breakdown boon for diabetics

WASHINGTON (TIP): In a ray of hope for millions of people suffering from type 2 diabetes worldwide, researchers have discovered a molecule that inhibits the breakdown of insulin in mice. The compound blocked a protein called insulindegrading enzyme (IDE) in mice. “If you inhibit the enzyme that breaks down insulin, insulin levels in your body should be higher and your blood glucose should be lower,” said David Liu, a chemical biologist at Harvard University in Cambridge, Massachusetts.

Since people with type 2 diabetes tend to have low insulin levels, it could lead to new ways of treating the disease, he noted. IDE has proved difficult to inhibit. Liu, along with his colleague Alan Saghatelian, screened a wide range of molecules that are both stable and specific.

They then tested the effects of the strongest candidate molecule in lean and obese mice given glucose. As expected, blood sugar levels dropped faster in those that received the inhibitor than in control mice, whether the mice were lean or obese.

The team also found something surprising: the IDE inhibitor had the opposite effect when the mice were injected with glucose rather than ingesting it. The reason for the different responses could be that IDE also affects two other gut hormones that regulate blood sugar – amylin and glucagon. For example, mice that received the inhibitor had higher levels of glucagon, a hormone that boosts blood sugar levels following glucose injection.

However, according to Liu, mice that ingest glucose tend to have much higher insulin levels than mice that are injected with it. “You could probably aim for a short lived IDE inhibitor that is taken before a meal,” Liu concluded in the study published in the journal Nature.

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