Higher-than-normal amounts of a selenium-containing enzyme could promote type 2 diabetes

A study by researchers at Cornell University suggests that higher-than-normal amounts of a selenium-containing enzyme could promote type 2 diabetes. The researchers found that mice with elevated levels of the antioxidant enzyme develop the precursors of diabetes at much higher rates than did control mice.

Selenium, a common dietary supplement, is an antioxidant, materials that help mop up harmful free radicals, molecules that can damage cell membranes and genetic material and contribute to the development of cancer and heart disease. Many of the benefits of selenium are related to its role in the production of glutathione peroxidase (GP), an antioxidant enzyme that helps detoxify the body.

"Although free radicals are known to be harmful and antioxidants helpful, our study suggests that we actually need some free radicals to regulate insulin sensitivity," says Xingen Lei, associate professor of animal science at Cornell and an author of the study, published in the June 15 issue of the Proceedings of the National Academy of Sciences, and now available online. The lead author is James McClung, who received his Ph.D. from Cornell this spring and is now a diabetes researcher at a U.S. Army laboratory in Boston.

The researchers found that mice that were bred to overexpress GP to up to three times above normal developed hyperglycemia, hyperinsulinemia and elevated plasma leptin, and became 36 percent heavier and twice as fat as did control mice. These conditions precede the development of type 2 diabetes.

GP, which holds about 60 percent of the selenium in the body, is the most abundant selenium-containing protein in mammals.

"These findings suggest a new cause of insulin resistance and argues against the general belief that antioxidants are beneficial to insulin function," says Lei, who notes that this is the first study to show that an antioxidant actually promotes insulin resistance, a precursor of type 2 diabetes. "Although antioxidants are beneficial for health, too many may be harmful and we need to be much more cautious in making recommendations to supplement the diet with them," adds Lei.

Type 2 diabetes is one of the fastest growing and most costly disorders worldwide, the scientists report, and insulin resistance is considered a hallmark of the disease.

McClung notes that high levels of GP appear to promote diabetes by mopping up too many free radicals, which are needed to help switch insulin signaling on and off in glucose (blood sugar) metabolism.

"Most people believe that both selenium and the selenium-containing enzyme GP are good for health by protecting cells and tissues from oxidation. However, this study suggests that they are a double-edged sword," says Lei. "Antioxidants can be harmful by neutralizing too many free radicals and interfering with insulin signaling, which results in promoting obesity, insulin resistance and possibly diabetes."

He points out that these findings are consistent with a recent study of pregnant women that reported on a link between high levels of GP, insulin resistance and gestational diabetes.

"Before people blindly supplement their diets with antioxidants, such as selenium and vitamins E and C, more research is needed," he concludes. Next, Lei plans to put the obese mice from this study on a diet to see if weight loss and fat loss can prevent or improve the mice's insulin sensitivity.

Other authors of the study are Donald Lisk, a toxicologist and Cornell professor emeritus of horticulture, research support specialist Carol Roneker, Cornell graduate student Weipeng Mu and Paul Langlais and Feng Liu of the University of Texas Health Science Center-San Antonio . McClung presented the research to the Experimental Biology 2004 meeting in Washington, D.C., in April and received first prize from the American Society of Nutritional sciences in a graduate student competition award.

The study was funded in part by the National Institutes of Health.