Blocking an enzyme combats disease

From Orlando, Fla., at a meeting of the American Diabetes Association

Scientists have extended the life of a compound important for metabolism by obstructing an enzyme that breaks it down. Called glucagon-like peptide 1 (GLP1), the beneficial compound stimulates the release of insulin from the pancreas and maintains insulin-making beta cells housed in that organ.

Unfortunately, GLP1 has a short life span. Once intestinal cells release the compound into the blood, it lasts only about 90 seconds before the enzyme, known as dipeptidyl peptidase-4 (DPP-4), breaks it down. Tests in animals have shown that knocking out DPP-4 permits GLP1 molecules to last longer, a change that improves sugar metabolism. In another approach, drugs that mimic GLP1 are proving useful in combating diabetes in tests on people (SN: 8/16/03, p. 104: Available to subscribers at Blood Sugar Fix).

Now, a team of European researchers has given an experimental drug that blocks DPP-4 to 32 people with type 2, or adult-onset, diabetes. A similar group of 26 patients received inert pills. All the patients had been taking the diabetes drug metformin, also called Glucophage, for 3 years and continued to do so during the trial.

After a year, there was a “marked difference” between those patients getting the experimental drug and those receiving the placebo, reports Bo Ahrén of Lund University in Sweden. Not only did those taking the DDP-4 blocker maintain control over their blood sugar concentrations, they also showed signs of improved beta-cell function in the pancreas. Both measures deteriorated in the placebo group.

The experimental enzyme blocker, dubbed LAF237, showed no significant side effects, Ahrén says.

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