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Protein removal reverses insulin resistance in diabetic mice

US researchers have reversed insulin resistance and glucose intolerance in mouse models of obesity and diabetes, according to a new report.
Scientists at the University of California School of Medicine have shown that genetically removing a protein called galectin-3 (Gal3) or targeting it with drugs can return insulin sensitivity and glucose tolerance to normal.
“This study puts Gal3 on the map for insulin resistance and diabetes in mouse model,” said lead author Dr Jerrold Olefsky. “Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach.”
When Gal3 binds to insulin receptors on cells, it prevents insulin from attaching to the receptors which leads to cellular insulin resistance. The protein has previously been connected to other diseases such as non-alcoholic steatohepatitis as well as heart and liver fibrosis.
In this study, Olefsky’s team investigated how chronic tissue inflammation leads to insulin resistance in type 2 diabetes. They observed that macrophages, a specialised type of white blood cell that destroys targeted cells, has a key role in inflammation.
They also found that Gal3 is secreted by macrophages, and this stimulates further production of the protein which leads to insulin resistance in liver, fat cells and muscle cells independent of inflammation.
Furthermore, bone marrow-derived macrophages were identified as the source of Gal3.
When Gal3 was targeted by pharmaceutical inhibitors or removed entirely, it reduced insulin resistance and improved glucose tolerance, even among older mice. Obesity, though, remained unchanged.
“These observations elucidate a novel role for Gal3 in insulin resistance, suggesting that Gal3 can link inflammation to decreased insulin sensitivity,” said the researchers. “Inhibition of Gal3 could be a new approach to treat insulin resistance.”
Benedict Jephcote, Head of Education at Diabetes.co.uk, said: “One thing to bear in mind is that there’s a hypothesis that insulin resistance may serve a partly protective purpose, such as to hold back insulin from leading to excessive fat storage.

“Therefore, while preventing insulin resistance alone may address some problems, such as high blood sugar, it may leave other problems unaddressed.”
The findings appear in the journal Cell.

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