Insulin may trigger type 1 diabetes.

Researchers have long puzzled over what causes the body to turn against itself in type 1 diabetes, an autoimmune disease that destroys insulin-secreting cells in the pancreas. Now, two studies suggest that insulin, a hormone that regulates blood sugar concentrations, may itself be to blame.

Insufficient amounts of insulin clearly lead to the symptoms of type 1 diabetes, but researchers haven't known whether the hormone directly sets the immune system on its course to creating the disease. Other molecules, such as the enzyme glutamic acid decarboxylase, may also play pivotal roles in this process, and any of these could become targets for new drugs.

"We know there are many targets in type1 diabetes," says George Eisenbarth of the University of Colorado Health Sciences Center in Denver. "The fundamental question is whether any one target is more important than any other."

Eisenbarth and his colleagues worked with mice genetically predisposed to develop type 1 diabetes even though the animals initially produce insulin. The researchers engineered some of the mice to produce an altered form of insulin that could regulate blood sugar yet remain below the immune system's radar screen. While the diabetesprone mice with normal insulin eventually developed the disease, those engineered to make altered insulin did not.

In the second study, David Hailer and his colleagues at Harvard Medical School in Boston isolated immune cells from patients with type 1 diabetes and analyzed the proteins that the cells latched onto. Half the isolated cells reacted to insulin, while immune cells from people without diabetes ignored the protein, the researchers found.

Both studies appear in the May 12 Nature.--C.B.