Removing a protein reverses insulin resistance in diabetic mice

UCSD

A UC San Diego-led team studying chronic inflammation and Type 2 diabetes has discovered that removing the protein galectin-3 from mice can reverse the insulin resistance and glucose intolerance that come with diabetes and obesity.

The team removed galectin-3, or Gal3, from the mice either genetically or by using drugs, according to a statement. They were able to bring insulin sensitivity and glucose tolerance to normal levels, even in older mice. While this finding was encouraging for diabetes symptoms, removing the protein did not affect obesity.

The researchers pinpointed macrophages derived from bone marrow as the source of Gal3 that causes insulin resistance. Macrophages are the white blood cells that engulf and digest microbes and other foreign bodies. The accumulation of macrophages in the liver, fat cells and skeletal muscle cells leads to chronic inflammation and insulin resistance. The Gal3 released by macrophages drives insulin resistance by binding to insulin receptors on cells and barring insulin from attaching to them. But that’s not all: Gal3 also acts as a signaling protein, attracting more macrophages to the area, which then produce even more Gal3.

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“This study puts Gal3 on the map for insulin resistance and diabetes in mouse models,” said Dr. Jerrold Olefsky, a professor of medicine in the endocrinology and metabolism division at UCSD School of Medicine, in the statement. “Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach.”

Targeting Gal3 shows promise in Type 2 diabetes, but the protein has previously been linked to other diseases, such as nonalcoholic steatohepatitis and heart and liver fibrosis.

Meanwhile, University of Pennsylvania researchers are working on combating insulin resistance by shutting down a pathway that transports excess fat into skeletal muscle. They linked insulin resistance to elevated levels of branched-chain amino acids. These amino acids produced a compound that helps transport fatty acids into skeletal muscle. Blocking this compound could be one way to combat the transport of excess fat into the muscle and prevent insulin resistance.

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