Researchers ID Hormone That Regulates Fat in Cells
Finding could one day lead to treatments for diabetics
FRIDAY, Jan. 18, 2002 (HealthDayNews) -- Researchers have discovered that the hormone leptin acts to get rid of excess fat in the muscle tissue of laboratory mice, thereby decreasing insulin resistance.
This finding could one day lead to new treatments for obese people, who are at great risk of diabetes, the researchers say.
"We thought if we can figure out how leptin sensitizes people to insulin, maybe there would be new avenues for a drug that could prevent cardiovascular complications in people with obesity or diabetes, and even prevent obese people from becoming diabetic," says Dr. Barbara Kahn.
Kahn is senior author of the new study, chief of the endocrinology, diabetes and metabolism division at Beth Israel Deaconess Medical Center in Boston and professor of medicine at Harvard Medical School.
The study appears in the current issue of the journal Nature.
Joseph Vasselli, a research scientist at the Obesity Research Center at St. Luke's-Roosevelt Hospital in New York City, calls the research "quite basic and quite important."
"What they found is that leptin stimulates a signal which protects the muscle from fat being deposited," he says. "When fat is deposited in muscle, insulin resistance increases in muscles. This is one of the causes of elevated blood sugar in Type II diabetes."
But despite the significance of the findings, new treatments for people aren't likely to come any time soon, Vasselli adds.
Obesity and diabetes are inextricably linked. Obesity is the major risk factor for Type II diabetes, a devastating disease that affects 16 million Americans.
Both obese people and people with Type II diabetes are resistant to the actions of the hormone insulin. As a result, they have a much higher incidence of cardiovascular disease, including stroke, heart attacks, atherosclerosis and peripheral blood-vessel disease.
Insulin serves to usher glucose out of the bloodstream and into cells where it can be used as energy for the cells. When a person is insulin-resistant, the glucose stays in the bloodstream, which is what eventually leads to the cardiovascular problems.
Scientists have not been able to pinpoint the exact relationship between insulin resistance and obesity and diabetes. One hypothesis states that insulin resistance develops when excess fat is deposited where it shouldn't be (for example, liver and muscle cells rather than fat cells, which are designed to take fat.)
Kahn and her colleagues set out to study that hypothesis. They further hypothesized that leptin, a hormone most famous for its role in telling the body when to stop eating and when to eat more, worked through a specific pathway in the body to get rid of fat deposited in the wrong places.
"I was trying to figure out if we could find a pathway involved in leptin's effort to mobilize fat deposits," says Kahn.
The pathway that Kahn's team studied was AMPK or AMP-activated protein kinase, which is involved in the combustion of fatty acids. AMPK exists in every organism from yeast to mammals and has often been described as a fuel gauge -- it registers how much energy a cell has.
As it turned out, leptin injected by the researchers into laboratory mice did activate the AMPK pathway and, as a result, increased the burning of excess fat. This was true when the hormone was injected directly into the brain and when it was injected into the bloodstream, and therefore acted directly on muscle tissue.
In other words, leptin got rid of unwanted fat build-up in muscle tissue in the mice. This, in turn, lowered insulin resistance.
Though there's not likely to be a cure for diabetes or obesity in the near future, the finding does reveal possible targets for new drugs.
"I do think that the pathway is a very good drug target," says Kahn.
What to Do: To learn more about diabetes, visit the American Diabetes Association, or the National Institute of Diabetes & Digestive & Kidney Diseases.