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Protein Reduces Insulin Resistance in Mice

Could help treat Type II diabetes and obesity

MONDAY, July 30, 2001 (HealthDayNews) -- A protein described in two new studies appears to reverse resistance to insulin, the hallmark of Type II diabetes.

While the protein, called adiponectin, has been tested only in mice, the findings could someday help people with the disease. Type II diabetes, also known as adult-onset diabetes, occurs when cells become resistant to insulin. It accounts for up to 95 percent of the 16 million cases of diabetes in the United States.

The findings appear in the August issue of Nature Medicine.

In the first study, researchers at the Diabetes Research and Training Center at the Albert Einstein College of Medicine in New York focused on adiponectin's effect on the liver in diabetic and obese mice.

Senior author Philipp E. Scherer and his colleagues, who identified adiponectin several years ago, found adiponectin appeared to affect the liver's sensitivity to glucose levels, indicating when enough glucose is circulating in the body and halting the liver's production of glucose.

"That regulation is occasionally or quite frequently not properly maintained in a diabetic state, because despite the fact that they have plenty of glucose or too much glucose sometimes, the liver continues to put out glucose," says Scherer.

"Adiponectin apparently is involved in sensitizing the liver to the actions of insulin, and that may be one of the beneficial aspects of this protein," he says. However, he says without insulin, adiponectin is not particularly effective.

"It seems like this particular protein, in some way that [we] still need to work out, stimulates or enhances the action of insulin with regards to the liver. The use of this protein might be pharmacologically applicable as an insulin-sensitizer," Scherer says.

Adiponectin also may act on other tissues, he says. "There is definitely something going on at the level of muscle," and it seems to play a role in the burning of fat, he says.

In a second study appearing in the same journal, researchers at the University of Tokyo found that adiponectin injections reduced blood glucose levels and insulin resistance in obese mice with a high-fat diet and in mice with reduced body fat. They also found it reduced fat levels in muscle tissue. As a result, the researchers concluded that adiponectin has potential as an anti-diabetic drug.

Alan R. Saltiel, a professor of medicine and physiology at the University of Michigan School of Medicine, in an accompanying commentary on both studies, says while adiponectin works on both the muscle and the liver, it's not clear whether what happens with the liver is an indirect effect through the muscle tissue.

"Either way, it's still potentially important," says Saltiel. He says adiponectin could increase the basal metabolism rate, which could have important implications for fighting obesity.

Both Saltiel and Scherer caution that adiponectin has been tested only in mice. There's little data on potential side effects, and Saltiel says human testing could be years away.

Scherer also says using a protein as a drug would be difficult. Like insulin, it would have to be injected, but it also appears to be an abundant protein, suggesting that it would require large doses. To avoid this problem, he says it may be better to stimulate the body's own production of adiponectin.

Scherer says adiponectin won't replace insulin, "but we may find it a useful supplement to an insulin regimen." Measuring adiponectin levels also could help determine insulin sensitivity, he says.

Saltiel says new treatments for obesity and diabetes are badly needed.

"[Obesity] is an epidemic problem. Diabetes is also an epidemic, and I think we're desperately in need of new therapeutic approaches to both problems, which are, of course, intertwined," Saltiel says.

Age, obesity, a family history of diabetes and physical inactivity are risk factors for Type II diabetes. Blacks, Hispanics, Asian-Americans and Pacific Islanders face a higher risk for the disorder.

People with diabetes are at greater risk for heart disease, stroke, kidney failure, high blood pressure and nerve damage. Nearly 200,000 die as a result of the disease every year, making it the seventh leading cause of death in the United States.

What To Do: For more information on Type II diabetes, check the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association or the Canadian Diabetes Association.

SOURCES: Interviews with Philipp E. Scherer, Ph.D., assistant professor, Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, N.Y.; Alan R. Saltiel, professor, medicine and physiology, Life Sciences Institute, Departments of Medicine and Physiology, University of Michigan School of Medicine, Ann Arbor; August 2001 Nature Medicine
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