In people who have diabetes, the body's immune system attacks its own insulin-producing beta cells in the pancreas.

And once those beta cells are destroyed, they generally will not replenish themselves sufficiently, even if the autoimmune response is stymied.

But a team of researchers at the University of Pittsburgh School of Medicine has identified two proteins in the cell cycle that put the brakes on beta-cell replication.

By turning off those proteins, the team, led by Dr. Andrew F. Stewart, Pitt professor of medicine and chief of the Division of Endocrinology and Metabolism, thinks it eventually could help people with diabetes generate new beta cells and restore natural production of insulin.

Of course, new beta cells will not last long under attack from the autoimmune response. But the discovery does mark the latest in a series of notable advances in diabetes at Pitt, where researchers hope they've set the stage for new treatments and an eventual cure for diabetes.

Last January, a study co-authored by Nathalie M. Fiaschi-Taesch of Pitt's Division of Endocrinology identified two key proteins that produce beta cells in the pancreas. When cells of diabetic mice were genetically engineered to produce more of these proteins, their blood-sugar levels normalized.

Now Pitt has shown how to release the brakes on beta-cell replication.

In people who have diabetes, the body produces too little insulin -- the hormone that allows blood glucose to enter cells for use as energy. Without enough insulin, glucose levels can build in the blood to levels that, without treatment, can lead to health complications and death.

"It's now clear that both Type 1 and Type 2 diabetes are beta-cell deficiency diseases," Dr. Stewart said. "And while we work on making more beta cells, our colleagues are trying to tackle the autoimmunity problems that cause a reduction in their number. Ultimately, both issues have to be addressed to develop a cure for diabetes."

Dr. Stewart's team presented its findings Monday during the 69th Annual Scientific Sessions of the American Diabetes Association in New Orleans. An accompanying paper on the research will be published on the ADA's online journal, Diabetes.

As it turns out, beta-cell reproduction, even in normal people, is minimal. So people remain largely dependent on beta cells produced early in life to generate insulin throughout their lifetimes.

So Dr. Stewart's team sought to identify what part of the cell cycle blocks beta cells from replenishing themselves in the pancreas.

George Harb, a postdoctoral fellow in Pitt's Division of Endocrinology and lead author in the study, focused on three suspect proteins -- p107, p130 and the retinoblastoma protein known or pRB.

Dr. Harb genetically engineered mice to be deficient in individual proteins. He then watched to see if beta-cell production would increase, but without success. Next, Dr. Harb genetically engineered mice to be deficient in two of the three suspect proteins.

After three years of breeding mice without realizing beta-cell regeneration, Dr. Harb said he entered the lab one day and found robust production of new beta cells. "It was pretty shocking," he said.

As it turned out, removal of pRB and p130 from the process allowed beta cells to replicate 30 times faster than normal. It is those two proteins that serve as brakes in the beta-cell replication process.

The research was supported by grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the Don and Arleen Wagner and the Pam and Scott Kroh family foundations.