Fixing Inflamed “Pipes” Could Reduce or Prevent Diabetes

Each of us faces the risk of diabetes as we get older, even when otherwise in good health. Normal aging is associated with the disease, which represents a very heavy burden on individuals and health systems and is among the top ten causes of death worldwide. Diabetes mainly arises within the pancreas, the organ that regulates blood sugar levels by releasing insulin into the body. When something goes awry with the insulin-producing cells, called β-cells, the body has trouble managing its blood sugar. This is what we see in aging: β-cells start to fail and malfunction, with dangerous consequences for the body. Dr. Rafael Drigo believes this failure has to do with the interaction between β-cells and neighboring blood vessels through, specifically, vascular inflammation. His research aims to reveal the underlying cause of that inflammation and the hope for controlling diabetes it might offer.

The β-cells of the pancreas are organized into structures called islets of Langerhans. In aging adults, the blood vessels lacing the islets become inflamed. This may eventually trigger problems for the β-cells that, like a repetitive stress injury, worsen with time. However, reversing the inflammation of the vessels, or giving the structure brand new vessels, can rejuvenate the islet. As Dr. Drigo says of the diabetic pancreas, “This means the structure of the house is intact, it just needs new pipes.” To make the necessary renovations possible, he needs to identify the cause of the harmful inflammation. Dr. Drigo’s hypothesis involves a pro-inflammatory molecule called ApoC3. A lifetime of ApoC3 circulating in the blood could contribute to accumulated injury to blood vessels—and subsequent negative effects on β-cells. This makes his next move clear: “If I can significantly reduce the amount of ApoC3, I may be able to decrease inflammation and ameliorate or even prevent β-cell failure with age.”

His methods are a departure from a common approach in diabetes research, where pancreatic cells are studied mostly in vitro, isolated from signals coming from the brain, liver and the rest of the body. “But we need to see how they work in the body to understand how they fail in the body,” he explains. The best way to observe that in a live animal is, in fact, through the transparent cornea of the eye. After a minimally invasive surgery to implant pancreatic islet cells on the iris, blood vessels begin to grow, anchoring them in position. As the mice he is studying age, Dr. Drigo will be able to monitor the islets, watching how the blood vessel/β-cell relationship changes. He’ll see how individual cells of the islet are functioning, as well as track changes to the structure’s vessels. This environment will let him test the impact on aging islets of a treatment to decrease levels of the inflammatory ApoC3. “If they look better, then I’ll have a link between this molecule, β-cell function and diabetes.”

The fact that drugs to lower ApoC3 are already in development to treat other conditions could make Dr. Drigo’s research great news for diabetes treatment. The protein has been linked to metabolic and cardiovascular disorders, but, until now, no one has looked at ApoC3 from an aging/diabetes perspective. Dr. Drigo hopes these anti-inflammatory products could be reused in a clinical setting, without starting the long, costly drug development process from scratch. The paradigm shift his work could represent for diabetes research has the potential to impact many patients’ lives, and quickly.

Scientific title : Apoc3 Mediates Ageing Of The Vasculature Of The Islet Of Langerhans

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