Get Mutated

Insulin itself is the target of friendly fire from the immune system in Type I diabetes, new research shows. The discovery may one day help doctors forestall that attack and thus prevent the disease.

Type I diabetes, also called juvenile diabetes, occurs when T-cells of the immune system mistakenly recognise insulin-producing cells in the pancreas as foreign and destroy them. But researchers have not been sure which of several possible molecules actually triggers this case of mistaken identity.

A team led by George Eisenbarth at the University of Colorado Health Sciences Center in Denver, US, genetically engineered diabetes-prone mice to lack normal insulin genes. Instead, the researchers gave the mice a modified insulin gene that functioned normally as a hormone but lacked the structural feature of insulin usually recognised by the immune system.

Even though these mice carried all the same molecular targets - except insulin - as their unmodified kin, they did not develop diabetes, strongly implying that insulin is the crucial target of autoimmune attack (Nature, vol 435, p 220).
Knowing where to look

Human diabetics show evidence of a similar autoimmune response against insulin, though earlier clinicians had failed to find anti-insulin T-cells in blood samples drawn from diabetic patients. But researchers led by David Hafler of Harvard Medical School in Massachusetts decided to look where those cells would be most likely to accumulate - in the lymph nodes draining the pancreas.

The team obtained lymph nodes from patients during surgery or from organ donors after death and cultured the T-cells they contained. Pancreatic lymph nodes from three diabetic patients contained large numbers of insulin-recognising T-cells while lymph nodes near their spleen or the pancreas of three non-diabetics did not (Nature, vol 435, p 224).

Taken together, the two studies come very close to clinching the case against insulin in the onset of human diabetes, says Lisa Spain, director of immunology for the Type I diabetes programme at the US National Institute for Diabetes and Digestive and Kidney diseases in Bethesda, Maryland.

With this knowledge in hand, researchers can now begin searching for ways to block the immune system's inappropriate response to insulin. A drug that binds to the insulin-recognising receptor on T-cells, for example, might prevent them from mounting a response, says Spain.