Thursday, March 26, 2015

U-M researchers identify how amlexanox drug improves metabolism of sugar


Amlexanox (trade name Aphthasol) is an anti-inflammatory antiallergic immunomodulator used to treat recurrent aphthous ulcers (canker sores), and (in Japan) several inflammatory conditions. This drug has been discontinued in the U.S


Researchers at the University of Michigan have identified how a promising drug in clinical trials for the treatment of obesity and related metabolic disorders improves the metabolism of sugar by generating a new signal between fat cells and the liver.

In addition to illuminating how the drug, amlexanox, reverses obesity, diabetes and fatty liver disease, the findings suggest a new pathway for future treatments. The research was published Jan.12 in Nature Communications.

Investigators in the lab of Alan Saltiel, the Mary Sue Coleman Director of U-M's Life Sciences Institute, had previously discovered that this drug, which had been used in the treatment of asthma, also has the ability to cause weight loss and improve diabetes in obese mice.

The current study revealed that amlexanox exerts its effects through a specialized type of fat cell by increasing the level of a second messenger molecule called cAMP. In turn, cAMP increases the rate by which cells "burn" fat so that the animal loses weight. But amlexanox also triggers the release of the hormone interleukin-6 from these fat cells, which then travels in the circulation to the liver. In the livers of diabetic mice, interleukin-6 reduces production of glucose, so that overall blood sugar is lowered.

"We know that amlexanox works to reverse obesity and insulin resistance in part by resolving chronic inflammation and increasing energy expenditure, but that's not the whole story of the drug's effects," said Shannon Reilly, first author of the study. "Understanding how the drug also enables crosstalk between fat cells and the liver in obese mice allows us to see more of the amlexanox picture--and also sheds light on communication between different tissues in the body."

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