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Diabetes Health Center

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Key Unlocks Obesity/Diabetes Link

Blocking Inflammation Pathway May Keep Obesity From Causing Diabetes
WebMD Health News
Reviewed by Louise Chang, MD

Nov. 6, 2007 -- Obesity leads to insulin resistance and diabetes, but not if a key inflammatory pathway is blocked, mouse studies show.

Abdominal obesity is a key risk factor for type 2 diabetes. As people gain more and more belly fat, they become more and more resistant to insulin. Their bodies have to make more and more insulin to control their blood sugar. Eventually, they develop diabetes.

Why does this happen? Scientists have found that one of the body's chemical signals, called JNK1, is needed both for the accumulation of abdominal fat and for obesity-related insulin resistance. Mice lacking the JNK1 gene can eat a high-fat diet without getting fat and without getting diabetes.

But can you become obese without getting diabetes? The surprising answer seems to be yes.

That is, if the JNK1 signal is blocked in the bone-marrow-derived immune cells called macrophages but not in other tissues. The finding comes from mouse studies by University of California, San Diego researchers Jerrold Olefsky, MD, and colleagues.

Macrophages, the researchers find, need JNK1 to keep up a low-level, obesity-triggered inflammatory response throughout the body. It is this immune response -- not obesity itself -- that leads to insulin resistance and diabetes.

"If we can block or disarm this macrophage inflammatory pathway in humans, we could interrupt the cascade that leads to insulin resistance and diabetes," Olefsky says in a news release.

It's much easier to find a drug that affects bone-marrow-derived cells than it is to find one that affects other cells. The findings thus take researchers one step closer to a new class of diabetes-preventing drugs.

"We aren't suggesting that obesity is healthy, but indications are promising that, by blocking the macrophage pathway, scientists may find a way to prevent the type 2 diabetes now linked to obesity," Olefsky says.

The findings appear in the November issue of Cell Metabolism.

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