inflammation leads to insulin resistance in type 2 diabetes. By removing the protein galectin-3 (Gal3), a team of investigators
led by University of California School of Medicine researchers were able
to reverse diabetic insulin resistance and glucose intolerance in mouse
models of obesity and diabetes.
By binding to insulin receptors on cells, Gal3 prevents insulin from
attaching to the receptors resulting in cellular insulin resistance.
The team led by Jerrold Olefsky, professor of medicine in the
Division of Endocrinology and Metabolism at UC San Diego School of
Medicine, showed that by genetically removing Gal3 or using
pharmaceutical inhibitors to target it, insulin sensitivity and glucose
tolerance could be returned to normal, even among older mice. However,
obesity remained unchanged.
‘Protein galectin-3 (Gal3) inhibition in people could be an effective anti-diabetic approach, suggested a new study.’
"This study puts Gal3 on the map for insulin resistance and diabetes
in mouse model," said Olefsky, associate dean for scientific affairs
and senior author of the study. "Our findings suggest that Gal3
inhibition in people could be an effective anti-diabetic approach."
Olefsky and other researchers have been studying how chronic tissue
inflammation leads to insulin resistance in type 2 diabetes. In the
paper, published in the journal Cell
, researchers explain that inflammation requires
macrophages - specialized cells that destroy targeted cells. In obese
adipose tissue (fat), for example, 40 percent of cells are macrophages.
Macrophages in turn secrete Gal3, which then acts as a signaling protein
attracting more macrophages, thus resulting in the production of even
Furthermore, investigators identified bone marrow-derived
macrophages as the source of Gal3 that leads to insulin resistance. More
importantly, researchers found that Gal3 is secreted by macrophages,
and can then cause insulin resistance in liver, fat cells, and muscle
cells independent of inflammation.
Gal3 has previously been connected to other diseases. Olefsky will
continue to study Gal3 depletion as a possible therapeutic target for
nonalcoholic steatohepatitis as well as heart and liver fibrosis.