Surprise finding uncovers why diabetes leads to poor wound healing

Kathleen Blanchard's picture
Molecule makes it difficult for diabetic wounds to heal
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Anyone with diabetes knows how important it is to take care when a cut or diabetic ulcer appears on the skin. One of the leading causes of amputation for anyone with diabetes is poor wound healing. Now researchers understand what happens to the tiny blood vessels in the body when you have diabetes that can make wound healing so difficult in findings that the scientists say were "definitely surprising".

Molecule found that inhibits blood vessel growth for those with diabetes

Investigators from Beth Israel Deaconess Medical Center (BIDMC) discovered a molecule called PGC-1alpha has an opposite effect in certain cells for people with diabetes.

The molecule has the capability to sense injury in muscles and acts to aid the body in healing by growing new blood vessels (angiogenesis).

High blood sugar is known to cause microvascular (tiny blood vessel) disease and poor wound healing for diabetics, but until now no one understand how it happened.

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“Diabetes is the number one cause of amputations in the U.S.,” explains senior author Zoltan Arany, MD, PhD, an investigator in BIDMC’s CardioVascular Institute and Associate Professor of Medicine at Harvard Medical School (HMS) in a press release. “While it’s been believed that high levels of glucose were somehow to blame for the inability of chronic ulcers and infections to properly heal in these patients, it wasn’t completely understood how this was happening.”

Caution urged for drugs that stimulate PGC-1 alpha

Arany explained: "In muscle cells, we’ve found that PGC-1alpha is pro-metabolic, and a critical regulator of angiogenesis. But the key cells responsible for carrying out angiogenesis are the endothelial cells that line the blood vessels. We, therefore, decided to investigate the role of endothelial PGC-1 alpha in diabetes.”

The researchers performed their investigation in cell cultures and in mouse models revealed PGC-1alpha has a completely opposite effect in endothelial cells than in muscle cells to prevent wounds from healing. The results showed high level of PGC-1 alpha is induced by high blood sugars.

The finding is also significant for understanding how designing drugs that target PGC-1 alpha could lead to harm. One area being studied currently is medications that target the molecule to treat Parkinson's disease. Another such drug that targets PGC-1 is Avandia that was pulled from the European market and is now restricted for use in the United States because of increased risk of heart attack.

“This isn't just interesting and paradoxical, it’s a potentially very important finding that reminds us that the same molecule can do different things in different cell types,” adds Arany. PGC-1 alpha was considered a 'good' molecule that promotes health. Now researchers have shown it can cause significant health problems when it is activated in endothelial cells; especially for people with diabetic wounds.

Reference:
Cell Metabolism, Volume 19, Issue 2, 246-258, 4 February 2014

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