Blocked. The ISO-1 compound (gray) blocks MIF in this structural representation.

Immune Factor Linked to Type 1 Diabetes

There may be a new kid on the block when it comes to understanding juvenile (Type 1) diabetes. A protein produced by the immune system plays a critical role in the development of the disease and represents a novel potential target for treatment, new research suggests.

In Type 1 diabetes, the immune system attacks the body, destroying pancreatic b cells and preventing the pancreas from producing the insulin. Without insulin, the body is unable to process glucose from food, which can lead to problems such as heart and kidney damage, or even coma. Prior research has shown that macrophage migration inhibitory factor (MIF)--a protein that helps regulate immune and inflammatory reactions--is elevated in people with autoimmune diseases like multiple sclerosis and colitis. This caused Yousef Al-Abed, a medicinal chemist at the Institute for Medical Research of the North Shore-Long Island Jewish Health System in Manhasset, New York,, and colleagues to wonder about MIF's role in another autoimmune condition, Type 1 diabetes.

The researchers tested their hypothesis by injecting a control group of mice with a diabetes-inducing compound called streptozotocin and a second group with the same compound plus ISO-1, a MIF-inhibitor developed by the team. While mice that received ISO-1 remained healthy, the control group developed high blood sugar—a key marker for Type 1 diabetes. In addition, the pancreases of the mice receiving ISO-1 showed much less β-cell destruction than the control group, the team reports online this month in the journal Endocrinology.

To determine whether MIF plays a role beyond the initiation of diabetes, the team also took a group of streptozotocin-treated mice and waited until they developed high blood sugar levels before treating them with ISO-1. After the mice received the MIF inhibitor, their blood sugar levels returned to normal, indicating that MIF is also pivotal in the progression of the disease. And in a follow-up study presented at the American Chemical Society meeting in San Diego, California, this month, Al-Abed and colleagues demonstrated that mice lacking the MIF gene remained healthy after being injected with streptozotocin.

Although past studies have shown correlations between MIF activity/level and Type 1 diabetes, this is the first in vivo study that shows the connection, says Abhay Satoskar, an immunologist at The Ohio State University in Columbus. Researchers now need to evaluate MIF levels in human diabetics to establish clinical relevance, he adds.

Related sites
The study
American Diabetes Association

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