Leptin could combat type 2 diabetes

University of Florida researchers have discovered the appetite-controlling hormone leptin could also combat type 2 diabetes, a disease that has become a growing problem in the United States as more Americans pack on extra pounds.

Using a novel gene therapy technique, UF researchers were able to reverse type 2 diabetes in mice. The researchers found that in diabetic mice, leptin acts in the hypothalamus to keep the body from producing too much insulin even after constant exposure to a high-fat diet, which over time can lead to or worsen type 2 diabetes, according to findings published this month in the online edition of the journal Peptides.

Although more tests are needed, scientists are hopeful these findings will lead to better treatments for patients with type 2 diabetes, said Satya Kalra, Ph.D., a UF professor of neuroscience and the senior author of the article.

"We found that we were successful in keeping the blood levels of insulin low at the same time keeping blood glucose levels at a normal range," Kalra said. "In other words, we were able to correct diabetes in these animals under various challenges."

The researchers injected a gene embedded in a harmless virus into the brains of the mice to increase leptin production in the hypothalamus, which regulates the hormone. While past studies have shown leptin acts in the brain to regulate weight and appetite, this is the first time researchers have shown that leptin can independently affect insulin secretion as well, Kalra said.

Typically, eating rich and fatty foods causes blood sugar levels to rise, which in turn causes the body to produce more insulin, a protein that helps the body use carbohydrates. Patients with type 2 diabetes often become resistant to the insulin they do make, causing too much of it to build up in the body. After gene therapy, tests showed that the blood sugar and insulin levels in the mice that received it had returned to normal, even when they were fed a high-fat diet. Mice that ate a high-fat diet but that did not receive gene therapy, however, continued to overproduce insulin and have high blood sugar levels, which Kalra said are markers for type 2 diabetes. In another arm of the study, researchers also discovered that normal, nondiabetic rats that received leptin gene therapy produced lower levels of insulin as well.

"This was totally unexpected," Kalra said. "Until now there was no evidence that leptin action in the hypothalamus had control on insulin secretion. (With leptin gene therapy) we can reimpose that control."

More than 18 million people in the United States have diabetes and about 90 percent of them have type 2 diabetes, also called adult-onset diabetes, according to the Centers for Disease Control and Prevention. Most cases of type 2 diabetes result from leading a sedentary lifestyle, being overweight and overeating.

If left untreated, type 2 diabetes can also cause cardiovascular disease, kidney disease and blindness.