New research from Denmark adds further weight to the idea that type 2 diabetes is an inflammatory disease.

The recently published study describes how in mice, during the very early stages of type 2 diabetes, immune cells called macrophages invade pancreatic tissue, releasing large quantities of cytokines - pro-inflammatory proteins - that help destroy insulin-producing beta cells.

More than 360 million people around the world have type 2 diabetes, including around 8% of Americans. The disease can lead to more serious conditions like cardiovascular disease, blindness, loss of limbs, and kidney failure.

In people who are healthy and do not have diabetes, the beta cells of the pancreas secrete insulin into the bloodstream - this helps to regulate blood sugar levels which rise after eating.

One of the researchers, Dr. Alexander Rosendahl, from the Department of Diabetes Complication Biology at Novo Nordisk A/S, in Malov, says:

"The study may provide novel insights allowing development of tailor-made anti-inflammatory based therapies reducing the burden of type 2 patients."

Such new treatments could be used to complement existing therapies, for example those that use insulin analogues, he adds.

For their study, Dr. Rosendahl and colleagues compared obese mice that spontaneously developed diabetes to normal healthy mice.

They observed the mice from a young age, when in early stages of obesity, until after their obesity in adulthood had started to affect multiple organs.

They monitored presence of macrophages around the insulin-producing beta cells of the pancreas, and also in the spleen. The advanced cytometric technology they used allowed them to take measurements at the level of single cells.

Proinflammatory macrophages 'invade diabetic islets'

Their observations showed some significant differences in what happened to the islets of the pancreas (the

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In a study of obese mice in the early stages of diabetes, researchers found that immune cells called macrophages invaded pancreatic tissue and released high amounts of pro-inflammatory proteins that destroyed insulin-producing beta cells.
clusters of beta cells that make and release insulin) and the spleen between the diabetic mice and the healthy mice - both in the early stages when they were young and in the advanced stages, when they were older.

The authors write:

"Already at 8 weeks of disease, on average, 12 macrophages were observed in the diabetic islets, whereas only two were recorded in the nondiabetic littermates."

They note how in the older diabetic mice, the changes in the pancreas and spleen moved more toward a pro- inflammatory pattern:

"In late-stage diabetes, the cytokine signature changed toward a TGF-β-dominated profile, coinciding with a significant increase of galectin-3-positive macrophages in the spleen."

They say these findings show that proinflammatory macrophages invade diabetic islets.

Potential for tailored immunotherapy treatments for type 2 diabetes

Dr. John Wherry, deputy editor of the Journal of Leukocyte Biology that published the study, says:

"This study sheds light on how a key inflammatory cell is connected to disease and what might go wrong when someone has type 2 diabetes. The knowledge gained from such studies offers hope that new immune-based therapies could be developed to mitigate the severity of such dieseases."

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