Researchers at the University of California, San Diego, believe they have discovered the "root cause" of Type 2 diabetes — a molecular link between obesity and diabetes that may lead to new treatment.
Inflammation that results from obesity leads to insulin resistance, the first step in developing Type 2 diabetes, the study found.
One inflammatory molecule in particular, LTB4, is released by immune cells living in extra fat, called macrophages. Positive feedback then signals for the body to release more macrophages, which then release more LTB4 into the fatty cells in the liver, researchers found.
"This study is important because it reveals a root cause of type 2 diabetes," the study's senior author Dr. Jerrold M. Olefsky, professor of medicine and associate dean for scientific affairs, said in a statement. "And now that we understand that LTB4 is the inflammatory factor causing insulin resistance, we can inhibit it to break the link between obesity and diabetes."
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Those LTB4 then bind to nearby cell surfaces, the researchers found. In people who are obese, those cells become inflamed and the body becomes resistant to insulin.
In the UC San Diego study, Olefsky and his team of researchers used genetically engineered mice to look for ways to reverse insulin resistance.
The team created genetically engineered mice that did not have the LTB4 receptor. Without the receptor, the health of obese mice “dramatically improved.”
The study was authored by Pingping Li, Da Young Oh, Gautam Bandyopadhyay, William S. Lagakos, Saswata Talukdar, Olivia Osborn, Andrew Johnson, Heekyung Chung, Rafael Mayoral, Michael Maris, Jachelle M Ofrecio, Sayaka Taguchi, Min Lu. All of the researchers are at UC San Diego.
The research was funded in part by the National Institute of Diabetes and Digestive and Kidney Disease, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Merck Inc.