Cells in our body are constantly churning out poisonous forms of oxygen (oxidants) and mopping them up with a countervailing force of proteins and chemicals (anti-oxidants).This balancing act of oxidative stress is particularly likely to go haywire in beta cells, the insulin-producing cells that malfunction and then start to die off in type 2 diabetes. Scientists at Joslin Diabetes Center now have found that a relatively little-studied enzyme plays a central role in defending beta cells against oxidants, but is damaged by the high levels of blood glucose produced in diabetes. Joslin Principal Investigator Robert Stanton, M.D., who led the research, says the discovery raises hopes of finding drugs that protect the enzyme, and thus the beta cells and their insulin production. Such drugs could help to stem the tide against type 2 diabetes, which now afflicts more than a quarter of a billion people worldwide. Scientists in the Stanton lab previously had found that lowered activity of the enzyme G6PD, the main producer of an antioxidant called NAPDH, can inflict damage on several cell types.The Joslin team went on to demonstrate that increases in the level of blood glucose cause a decrease in NAPDH that ends up killing beta cells-and that increasing the level of this antioxidant guards against this effect, at least in mouse beta cells. “Preventing the death of beta cells or stimulating beta cells to grow is a kind of Holy Grail in diabetes prevention,” Stanton notes. “Treatments aimed at increasing this essential antioxidant hold great promise for treating or preventing diabetes in people.”If this approach is successful, it could prove important for other illnesses as well. Abnormally high level of oxidants are thought to be a major cause of kidney disease, heart disease, hypertension, Alzheimer’s disease and many other conditions. “I hope that a new era of highly specific, targeted treatments will emerge that very effectively treat or possibly prevent many of these diseases,” Stanton says. This new discovery brings scientists one step closer to finding a cure for diabetes by finding its root cause.The study has been published online in the FASEB Journal.
