Diabetes from a plastic? Estrogen mimic provokes insulin resistance.

Exposure to small amounts of an ingredient in polycarbonate plastic may increase a person's risk of diabetes, according to a new study in mice.

The synthetic chemical called bisphenol-A is used to make dental sealants, sturdy microwavable plastics, linings for metal food-and-beverage containers, baby bottles, and numerous other products. When consumed, the chemical can mimic the effects of estrogen. Previous tests had found that bisphenol-A can leach into food and water and that it's widely prevalent in human blood.

The newfound contribution of the chemical to insulin resistance, a precursor to diabetes, might partially explain the global epidemic of that disease, says Angel Nadal of Miguel Hernandez University of Elche in Spain, who led the new study.

The finding is a "wake-up call" for public health researchers who are concerned by the prevalence of diabetes, comments developmental biologist Frederick vom Saal of the University of Missouri-Columbia.

Earlier test-tube studies had suggested that bisphenol-A makes pancreatic cells secrete the glucose-regulating hormone insulin. To investigate this effect in live animals, Nadal and his colleagues injected adult male mice with pure corn oil or with oil containing either bisphenol-A or an equal amount of the natural female sex hormone estradiol. Animals received as many as eight shots over 4 days.

Within 30 minutes of an injection, animals receiving either the sex hormone or bisphenol-A had abnormally low concentrations of glucose in their blood, Nadal's team reports in the January Environmental Health Perspectives. The chemicals acted on recently discovered estrogen receptors on pancreatic cells' surfaces to boost the cells' secretion of insulin, the researchers determined.

Repeated exposure to either bisphenol-A or the natural estrogen over several days produced insulin resistance, a pre-diabetic state in which tissues lose their sensitivity to normal concentrations of insulin, Nadal's group says. Estrogen receptors in the pancreatic-cell nucleus appear to contribute to this gradual effect.

So, receptors both in the cell nucleus and on the surface could contribute to insulin resistance and diabetes, Nadal says.

This risk could add to or elucidate already documented health effects of bisphenol-A. Animal studies have suggested that exposure to the chemical early in life causes obesity, says Ana M. Soto of Tufts University School of Medicine in Boston.

Furthermore, bisphenol-A exposure might contribute to gestational diabetes in women, in whom insulin resistance often increases during pregnancy, says Jerry Heindel of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C.

Inside cells' nuclei, bisphenol-A is less potent than the natural sex hormone, says vom Saal. But the new work shows that at the surface of pancreatic cells, the compounds have the same potency, he notes. Doses of bisphenol-A considered by the Environmental Protection Agency to have no adverse effect led to insulin resistance in the mouse study.