Fat cell defect may lead to insulin resistance and type 2 diabetes By Suzanne Rostler

NEW YORK, Feb 08 (Reuters Health) - Defective fat cells may be the key to understanding and treating type 2 diabetes, a disease that increasingly threatens the health of the nation, US scientists report.

Their study in mice suggests that type 2 diabetes and insulin resistance--a condition that often precedes diabetes--might occur when fat cells release a still unknown substance that prevents cells from responding to insulin, a hormone that helps regulate blood glucose (sugar).

The investigators suggest that this compound might also cause other types of cells, such as those in muscle and the liver, to ignore the command of insulin to remove sugar from the blood.

The preliminary findings, published in the February 8th issue of Nature, point to an important new risk factor for type 2 diabetes, which could be a target for preventing and treating the disease. The report also highlights the role that fat cells might play in the onset of diabetes. Previously, it was assumed that the uptake of sugar into muscle cells was the key to preventing diabetes.

"This whole concept is extremely exciting in terms of the possibility of finding new drug targets for reducing insulin resistance, improving blood sugar control, or even decreasing the possibility of developing diabetes," Dr. Barbara B. Kahn, a study author from Harvard Medical School in Boston, Massachusetts, said in a prepared statement.

The researchers disabled a protein in fat cells that transports glucose into cells. Cells in the liver and in muscles also ignored insulin, possibly due to a compound that is released by fat cells and travels to other body tissues. Over time the mice became insulin-resistant, a condition that usually occurs in obese people and is a first step toward diabetes. Some mice developed very high blood glucose.

"Specifically reducing the capacity of the fat cell to take up sugar in response to insulin leads to an increase in the production of the mysterious factor, which impairs insulin action in muscle and fat," explained Dr. Morris J. Birnbaum in an interview with Reuters Health. Birnbaum, from the University of Pennsylvania School of Medicine in Philadelphia, authored a News and Views article accompanying the report in Nature.

"This dramatically emphasizes the fat cell as a likely primary source of much of the abnormalities in insulin action seen throughout the body in type 2 diabetes," he said.

Type 2 diabetes occurs when cells fail to respond to insulin, and glucose in the blood rises to levels that can--over time--increase patients' risk of developing heart disease, kidney failure, nerve damage and blindness. More than 14 million Americans are estimated to have the disease and one third of these are believed to be undiagnosed, according to the American Diabetes Association.

The study adds to a growing body of evidence that suggests a role of fat cells in type 2 diabetes. In January, researchers identified a hormone in mice that is released by fat cells and appears to cause cells to resist or ignore insulin, thereby increasing the risk of diabetes. The hormone, named "resistin" after the mechanism by which it is thought to work, has also been identified in humans.

The current study "strengthens the idea that fat cells are capable of communicating with other organs in the body, in particular muscle and fat," Birnbaum said.

Identifying the means by which fat cells communicate will be a next step in developing new treatments. But these treatments are still years away, he added.

SOURCE: Nature 2001;409:672-673, 729-733.