THURSDAY, May 15, 2003 (HealthDayNews) -- Power shortages in the body's cells may contribute to insulin resistance and, eventually, the development of type 2 diabetes in elderly people.
Researchers reporting in the May 16 issue of Science say that problems with mitochondria, which are the cell's energy centers, may be at the root of insulin resistance, which is a defining characteristic of type 2 diabetes.
The discovery could eventually lead to new drugs for type 2 diabetes, which is affecting a growing number of Americans, particularly older ones.
"These advances are very important for us to understand why certain things happen," says Dr. Edmund Giegerich, an endocrinologist and executive vice president for medical affairs at Long Island College Hospital in New York City. "The application will obviously come when someone can produce a medication that will affect mitochondrial function."
About 25 percent of Americans over the age of 60 suffer from type 2 diabetes, which occurs when the body's insulin fails to function properly. Under normal circumstances, insulin, a hormone produced by the pancreas, is responsible for ushering glucose out of the blood stream after people eat. Once glucose and fatty acids are safely inside the cell walls, mitochondria convert them into energy through the process of oxidation.
When insulin isn't doing its job, however, glucose remains in the blood stream and, after prolonged periods of time, can result in such complications as blindness and kidney failure.
Dr. Gerald I. Shulman, senior author of the new study and an investigator at the Howard Hughes Medical Institute in Chevy Chase, Md., had already discovered that an accumulation of fat in muscle and liver tissue could lead to insulin resistance in those same tissues.
The question he needed to answer was what was behind the accumulation of fat. Shulman, who is also a professor at Yale University School of Medicine, figured the answer lay in one or both of two processes: that fat cells were releasing more fatty acids than necessary or there was a problem with the mitochondria's break-up of fatty acids.
To figure out what was going on, the researchers decided to compare glucose and fatty acid metabolism in healthy elderly people with young adults. The two groups were matched for lean body mass as well as fat mass, so these factors could not affect differences in insulin resistance.
The elderly participants turned out to be more insulin-resistant, especially in muscle tissue, than the younger participants. Magnetic resonance spectroscopy revealed that the older group also had higher levels of fat in the muscle tissue.
When the researchers looked more closely, they discovered that the fat cells were not releasing the extra fat building up in the muscle. In fact, mitochondrial activity was reduced by about 40 percent in the older group of participants.
"At least in the elderly, it looks like it's mitochondrial dysfunction that leads to the accumulation of fat inside the cells of muscle and livers," Shulman explains. "That then leads to insulin resistance through pathways we've described previously."
Part of the significance of the study is in its specificity.
"This really helps pinpoint where one would now try to focus on improving mitochondrial oxidative function," Shulman says. "The next question is why is mitochondrial function down? Is it simply a reduced number or is it actually something wrong with each individual mitochondria?"
Shulman also wants to know if similar defects are occurring in the insulin-resistant offspring of parents with type 2 diabetes.
"You can be in your 20s and be lean and have the same type of insulin resistance as we're seeing in the elderly," he says. "They also have an accumulation of fat in muscle and the same question exists: Is it due to abnormalities in fat cells or defects in mitochondrial function?"
Some good news is that researchers have already shown that exercise can increase the number of mitochondria. Until new medications are developed, this study is yet another argument to get moving.
More information
For more information on type 2 diabetes, including insulin resistance, visit the American Diabetes Association or the National Institute of Diabetes & Digestive & Kidney Diseases.
