Activated Protein C might protect kidneys from diabetes

Kidney disease is a leading cause of premature death in diabetics, but new research from the Oklahoma Medical Research Foundation could change that.

Diabetes affects 25.8 million Americans, including 296,000 Oklahomans. Normally, cells use a hormone called insulin to turn glucose—a type of sugar created by the body when it processes food—into energy. But diabetic patients’ bodies don’t make enough insulin or become insulin-resistant, so they can’t process the glucose.

Another side effect of the disease is high blood sugar, which can overwork the kidneys and lead to eventual kidney failure. This disease, called diabetic nephropathy, is irreversible and is a leading premature killer of diabetics.

In a paper published in the journal Proceedings of the National Academy of Sciences, OMRF scientist Charles Esmon, Ph.D., shows that activated Protein C (or APC) reduces the effects of a protein that kills kidney cells.

“We’ve known for a while that thrombomodulin, which causes protein C activation, is down-regulated in diabetes—which means it doesn’t make as much as in people without diabetes,” said Esmon, who holds the Lloyd Noble Chair in Cardiovascular Biology at OMRF.

In previous experiments, Esmon and Berend Isermann, Ph.D., Director of Medicine and Clinical Chemistry at the University of Heidelberg in Germany, showed that increasing APC in a mouse model of diabetes reduced the amount of cell death caused by the disease.

In patients with diabetic nephropathy, an enzyme called p66 causes damage to kidney cells and signals for them to die, Esmon said.

“We’ve nicknamed it ‘Dr. Death,’” he said. “What we have found is that the high glucose levels found in the diabetic patients increase p66 or Dr. Death and that APC prevents this increase thereby protecting the kidney cells.”

Because APC is also an anti-coagulant, or blood thinner, it can’t be used frequently without causing other complications, he said. But the scientists are now searching for a mutated form of APC which would have the same benefits to the kidneys without causing bleeding.

Funding for the research was provided by the Howard Hughes Medical Institute.

Esmon is involved in research collaborations looking at APC as a possible treatment for trauma, Crohn’s disease, stroke, and multiple sclerosis.