Insulin resistance – a condition where the body’s cells fail to respond normally to the glucose control hormone insulin – increases the risk of developing type 2 diabetes and prediabetes. Now, a team shows that removing or blocking a protein mainly secreted by immune cells reverses diabetic insulin resistance and glucose intolerance in obese and diabetic mice.
The team – including researchers from the University of California-San Diego (UCSD) – reports what it discovered about the protein galectin-3 or Gal3 in the journal Cell.
Senior author Jerrold Olefsky, a professor of medicine at UCSD School of Medicine, remarks:
“This study puts Gal3 on the map for insulin resistance and diabetes in mouse model.”
Insulin is a hormone that the body uses to control glucose or blood sugar. Diabetes is a chronic disease that arises either when the pancreas does not make enough insulin (known as type 1 diabetes) or when the body cannot use the insulin it produces properly (type 2 diabetes).
Until recently, type 2 diabetes was only seen in adults, but now more and more children are developing it.
If diabetes goes untreated, there is a high chance of hyperglycemia, or raised blood sugar, which over time causes serious damage to vital parts of the body, including nerves and blood vessels.
In 2014, global estimates suggest 8.5 percent of adults were living with diabetes – up from 4.7 percent in 1980. In 2012, an estimated 1.5 million people died as a direct result of diabetes, and another 2.2 million as a result of high blood glucose.
Rates of diabetes have been rising more rapidly in middle- and low-income countries. In the United States, rates of new cases of diagnosed diabetes have started to fall, but the numbers are still very high.
Over 29 million Americans are thought to have diabetes, and 86 million have prediabetes – a serious condition that raises the risk of developing type 2 diabetes and other chronic diseases.
- People with diabetes are
twice as likelyto have heart disease or a stroke as people without diabetes
- Up to 25 percent of American adults who have diabetes don’t know they have it or realize they could be developing serious complications
- More than a fifth of healthcare spending in the U.S. goes on people with diagnosed diabetes.
In the new study, he and his colleagues explain how immune cells called macrophages – which destroy targeted cells – play an important role in inflammation.
In obese humans and mice, macrophages and other immune cells accumulate in fat tissue. The researchers note that around 40 percent of cells in fat tissue in obese subjects are macrophages.
The high levels of these immune cells in the fat tissue promotes “a chronic inflammatory state and insulin resistance,” they write, adding that obese mice and humans also have high levels of Gal3 – a signaling protein secreted by macrophages.
The secretion of Gal3 attracts more macrophages, setting up a vicious cycle that results in ever-increasing levels of the signaling protein and accumulation of the immune cells.
In lab experiments, the researchers found that Gal3 was produced by bone marrow-derived macrophages and that secretion of the protein leads to insulin resistance in liver, muscle, and fat cells – even when there is no inflammation.
They also found giving mice Gal3 leads to insulin resistance and glucose intolerance, while blocking it in obese mice – either with drugs or by silencing a gene – improves insulin sensitivity.
Other studies have already linked Gal3 to other diseases. The team now plans to find out if the signaling protein could be a target for the treatment of conditions such as nonalcoholic fatty liver disease and heart and liver fibrosis.
“Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach.”
Prof. Jerrold Olefsky