Enzymes Help Restore Diabetic Kidney Function

A recent study shows how enzymes can help treat diabetic kidney disease.

According to researchers at the University of California, San Diego School of Medicine, they found that elevated cellular levels of glucose may ultimately result in diabetic kidney disease.

Current theory shows that impaired diabetic kidney function may suggest that humans as well as mice may result in chronically high glucose (sugar) levels that may prompt energy-generating mitochondria in cells that produce an overabundance of superoxide anion via a highly reactive and toxic molecule that ultimately leads to downstream cellular damage, disease and organ dysfunction.

Yet led study authors Kumar Sharma, MD, professor of medicine and director of the Center for Renal Translational Medicine (CRTM) at UC San Diego, Laura Dugan, professor of medicine and Larry L. Hillblom, Chair in geriatric medicine, worked to detect higher-than-normal levels of superoxide in the damaged kidneys of the diabetic mice as researchers worked to reduce superoxide production and suppress mitochondrial activity. As they stimulated the mitochondria by activating a key energy-sensing enzyme called AMPK, superoxide production increased. However, evidence of diabetic kidney disease markedly declined.

"Mitochondrial superoxide does not seem to be a causative factor of diabetic kidney disease," said Sharma. "Indeed, when mitochondrial superoxide is increased with AMPK activation, there is reduced kidney disease, suggesting that improving mitochondrial function and superoxide production is actually beneficial for diabetic complications. This idea is a sea change in the field of diabetic complications."

Researchers believe the problematic reduction in AMPK activity may be likely due to "caloric excess" that creates cellular imbalances that are often associated with inflammation and fibrosis.

"In addition, methods will need to be developed to monitor mitochondrial function in animal models and in clinical trials," said Sharma. "The study of metabolites may be of great value to monitor mitochondrial non-invasively. Other methods, such as novel imaging tools like the one described in our paper, will also be important to follow mitochondrial superoxide production. It's interesting to note that recent studies by other groups have suggested that stimulating mitochondrial superoxide production may actually increase longevity and contribute to the benefits of exercise."

More information regarding the study can be found via the Journal of Clinical Investigation.