Removing Protein Reverses Insulin Resistance in Mice

The study identifies a potential drug target to treat diabetes.

Researchers reversed insulin resistance and glucose intolerance in mice when they removed a key protein, suggesting it could be a target for drugs that would correct diabetes.

The team from the University of California at San Diego (UCSD) studied the effects of galectin-3, or Gal3, which prevents insulin from attaching to receptors, causing insulin resistance.

The researchers, led by senior author Jerrold Olefsky, MD, showed that when Gal3 was genetically removed or chemically blocked, the mice regained insulin sensitivity and glucose tolerance. Obesity, however, was unchanged.

“This study puts Gal3 on the amp for insulin resistance and diabetes in the mouse model,” said Olefsky, professor of medicine in the Division of Endocrinology and Metabolism and associate dean for Scientific Affairs at UCSD, in a statement. “Our findings suggest that Gal3 inhibition in people could be an effective antidiabetic approach.”

The findings appeared in the new issue of Cell.

Olefsky and his team have been studying the process of inflammation, which triggers insulin resistance in type 2 diabetes—the most common form of the disease, affecting more than 27 million people in the United States.

The paper in Cell explains the role of special cells called macrophages in inflammation; these cells secrete Gal3 in a snowball effect—the more Gal3, the more the protein attracts macrophages, which, in turn, secrete more of the protein. Researchers identify bone marrow as the original source of the macrophages, but note that they accumulate in fat tissue, which would explain why obesity is linked with type 2 diabetes.

Inhibition of the protein, by contrast, could treat insulin resistance and diabetes. The researchers note that Gal3 has been implicated in other diseases liked to inflammation.

Reference

Pingping L, Liu S, Lu M, et al. Hematopoietic-derived galectin-3 causes cellular and systemic insulin resistance. Cell. 2016;167(4):973. doi: 10.1016/j.cell.2016.10.025.