Researchers at the UCSD School of Medicine discovered a link between obesity and insulin resistance on Feb. 23. Published in Nature Medicine Magazine, their study explains how manipulating the inflammatory molecule LTB4 can prevent insulin resistance, which opens up a new potential pathway to solve epidemic diabetic problems.
Scientists were already aware of the fact that inflammation is directly related to insulin resistance. However, what researchers did not know was how to effectively prevent inflammation from causing insulin resistance. The study describes a new mechanism that blocks LTB4 from its receptors using small synthetic molecules called “LTB4 antagonists.”
Senior author of the study, Dr. Jerrold M. Olefsky, discussed how the test subjects did not show any signs of diabetes.
“When we treated animals with that compound, we produced everything we were hoping for,” Olefsky told the UCSD Guardian. “They didn’t develop diabetes. They didn’t develop insulin resistance. They didn’t develop inflammation. They were fine.”
Obesity expands adipose tissue with immune cells, causing chronic inflammation. In the meantime, LTB4 is released from the immune cells and binds to the receptors of other cells such as liver, fat and muscle cells. These cells eventually become inflamed and cause insulin resistance, which is the first step to Type-2 diabetes.
Researchers experimented on mice whose cell receptors were blocked from LTB4. According to Olefsky, this new mechanism prevents insulin resistance, Type 2 diabetes and the metabolically harmful effects of obesity by avoiding inflammation.
Pingping Li, who was on the research team, stated that the experiment may work on humans.
“In the animal work, we find that the effect is very dramatic. It’s a big effect,” Li said. “If we can find the same effect on humans, it would be a very big deal.”
According to Olefsky, safe synthetic molecules that can be applied to humans are currently unavailable.
“[The current synthetic molecule’s] half-life is way too long to use in people, and the doses are too high,” Olefsky said.
A pharmaceutical company is in the process of finding human-safe molecules. At first, the company will experiment on monkeys and eventually on human bodies, depending on the experiment’s safety and efficiency on monkeys.
If successful, the medication will prevent people from developing Type-2 diabetes and provide an effective treatment for people who have already developed the disease.
The ultimate goal of the research team is to focus on finding practical medical solutions for diabetes.
“If I could somehow help to develop a drug that treats diabetes, that certainly would be the long-range goal,” Olefsky said. “That would be the dream.”
