Investigators at the University of California-San Diego say they've identified a crucial link between obesity and diabetes, and now they're zeroing in on a new drug that can break it.
The culprit, say the researchers, is an inflammatory molecule dubbed LTB4. Blocking that molecule improved insulin sensitivity in mice and provided an early indication that they are on the right path.
The release of LTB4 is a natural response to an inflammatory provocation, which in the event of a transient infection would be a good thing. But with chronic obesity, the inflammation sets up a loop that continues to generate the molecule. Liver, fat and muscle cells become activated when LTB4 binds to them, activating and then provoking an inflammatory response in the cells that makes them insensitive to insulin--a key step in developing diabetes.
To test their theory, the team created a mouse model without LTB4 and found that improved the metabolic health of fat rodents. Then they used an existing drug that had been abandoned in clinical studies that blocked LTB4, and found that it worked as expected, preventing and also reversing insulin resistance.
"When we disrupted the LTB4-induced inflammation cycle either through genetics or a drug, it had a beautiful effect--we saw improved metabolism and insulin sensitivity in our mice," said Dr. Jerrold Olefsky, professor of medicine, associate dean for scientific affairs and senior author of the study. "Even though they were still obese, they were in much better shape."
- here's the release