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Fighting diabetes in fat mice

Twin brothers working in labs 2,260 miles apart are part of a team of scientists who found a simple way to reverse the effects of Type 2 diabetes, at least in mice. The key, they found, lies in the powerful T-cell, an immune system cell that plays an important role in both diabetes and obesity. Daniel Winer, MD, a postdoc at Stanford, says he and his brother, Shawn, at the Hospital for Sick Children in Toronto, noticed that overfed lab mice had an imbalance in their T-cells.

Normally T-cells are a good thing to have, as they protect the body from all kinds of infections. But these fat mice had a preponderance of inflammatory (bad) T-cells, which are attracted to fat tissue. These inflammatory cells caused the mice to lose their ability to sense insulin, thus leading to diabetes. Interestingly enough, a similar pattern of T-cell imbalance was found in some human fat samples, suggesting the process might be at work in people as well.

Remarkably, the team of scientists was able to reverse the diabetic disease in mice by using a drug to correct the T-cell imbalance. The drug, called anti-CD3, lessened weight gain, normalized insulin resistance and helped the animals gain control of their blood sugar levels. And these improvements continued, even though the animals lived on a super-high fat diet. The researchers published the results in the latest issue of the high-powered journal Nature Medicine.

"This concept that T-cells play a role in regulating a physiologic function like blood sugar levels and possibly other obesity-associated abnormalities is novel. It opens up a brand new way of thinking about these conditions to develop new treatments," said Daniel Winer, who works in the lab of pathology professor Ed Engleman, MD, at Stanford.

Shawn Winer, MD, PhD, the first author on the paper, is a postdoc in the University of Toronto lab of H. Michael Dosch, MD, PhD, who is the senior author. What is particularly exciting, the researchers noted, is that anti-CD3 is a well-known drug, having been used for years to prevent organ rejection in both adult and pediatric transplant patients. Now clinical trials in people are needed to determine if it can help humans with diabetes as much as it has helped mice.

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