Find May Lead To Diabetes Cure

While experts have long known that obesity and Type 2 diabetes are related, researchers at the Harvard School of Public Health (HSPH) believe they have found the biological mechanism which explains the connection—a breakthrough that could eventually lead to a new treatment for this form of diabetes.

For the past two years, Simmons Professor of Genetics and Metabolism Gokhan S. Hotamisligil has led a research team seeking the pathway through which excess body fat can result in diabetes.

Through experiments both on mice and isolated cells, the team discovered that excess fat stresses the endoplasmic reticulum (ER) of a cell, which is used to synthesize important proteins.

This stress causes the cell to go into survival mode, where it is less responsive to insulin and results in diabetes.

“In this study, we demonstrated perhaps the very first event which triggers this pathway is stress in the ER,” said Hotamisligil, who is also the chair of the Department of Genetics and Complex Diseases at HPSH.

Now that more is known about the causes of Type 2 diabetes, Hotamisligil said he hoped that researchers can find ways to lessen the stress on cells caused by excess body fat to prevent diabetes from occurring.

“Thinking optimistically, we see a wide array of previously unforeseen possibilities,” he said. “This is probably the kind of discovery which is more likely than others to lead to a type of treatment.”

It is estimated that 18 million in the United States have Type 2 diabetes—almost 95 percent of the total number of diabetics—and it kills 200,000 Americans each year.

When a person develops the disease, his or her body becomes resistant to insulin, preventing cells from processing the sugars they depend on for energy. This leads to high blood sugar levels, which can result in heart disease, stroke, kidney disease, blindness and the amputation of limbs.

Osama Hamdy—the director of the Obesity Program at the Joslin Diabetes Center, which is affiliated with the Harvard Medical School—has been working with diabetes for the past 24 years. He said that it has long been known that obesity and diabetes are related, and that they are both becoming greater problems. Over the past few years, he said, “the prevalence of diabetes went up exactly with the prevalence of obesity.”

“For the first time, they have some explanation of why the fat cells are changing. The study shows clearly that the ER is under stress with the accumulation of fat,” Hamdy said.

He said he also believes that the information from the HSPH study will be helpful in finding treatments for Type 2 diabetes, but cautioned that its application is “not in the very near future” because researchers are occupied with exploring other avenues.

Hotamisligil said he plans to continue working in this area. “We will follow up this observation...Within the connection of the biochemical pathways, there are still some gaps we are thinking of closing.”

Hotamisligil’s diabetes research is the latest project in a career spent working with diseases related to metabolism and weight issues.

“There is a clustering of problems around obesity, such as diabetes,” he said. “All of my work centers around understanding this clustering of metabolic diseases.”

Funding for the HSPH study came from the National Institutes of Health.