Leptin jabs restore full health to diabetic mice

Washington, August 26 : Scientists at UT Southwestern Medical Center have made a significance advance in restoring terminally ill rodents with type 1 diabetes to full health by injecting them with a substance other than insulin.

Describing their work in a paper published in the online edition of the Proceedings of the National Academy of Sciences, the researchers say that their progress suggests that insulin is not the only agent that is effective.

They add that leptin, a hormone produced by the body's fat cells, also lowers blood glucose levels, and maintains them in a normal range for extended periods.

"The fact that these animals don't die and are restored to normal health despite a total lack of insulin is hard for many researchers and clinicians to believe. Many scientists, including us, thought it would be a waste of time to give leptin in the absence of insulin. We've been brainwashed into thinking that insulin is the only substance that can correct the consequences of insulin deficiency," said Dr. Roger Unger, professor of internal medicine and senior author of the study.

The researchers have revealed that leptin appears to work by suppressing glucagon, a hormone produced by the pancreas that raises glucose levels.

In insulin deficiency, glucagon levels are inappropriately high, and cause the liver to release excessive amounts of glucose into the bloodstream.

During the course of study, the researchers for the first time tested whether or not a single injection of the leptin gene given to insulin-deficient mice and rats on the verge of death from diabetic coma could reverse the severe condition, and prevent the animals from dying.

They observed that the animals that were administered the therapy began producing excessive amounts of leptin, which reversed all the measurable consequences of type 1 diabetes, including weight loss, hyperglycemia and ketoacidosis, a potentially fatal condition that develops when the body doesn't have enough insulin to meet basic metabolic requirements.

Dr. Xinxin Yu, assistant instructor of internal medicine and lead author of the study, said that much of the effect was mediated by complete suppression of the high glucagon levels.

"These animals were actually dying. But if we gave them the leptin gene, within two weeks, the terminally ill rodents were restored to full health without any other treatment," Dr. Yu said.

Though the researchers concede that it is too premature to know whether leptin might someday replace insulin as a treatment for diabetic patients, Dr. Unger insists that the study shows that leptin could at least handle some of insulin's job requirements, and do it for longer periods of time.

"My hope is that you could give leptin for one type of action - glucagon's suppression, for example - and insulin for another. Or perhaps give a substance other than insulin entirely. What would be a tremendous advance would be the ability to give an oral agent that suppresses glucagon without injections," Dr. Unger said.

Some team members believe that leptin combats diabetes not only be suppressing glucagon's action on the liver, but also by boosting the insulin-like actions of IGF-1 (insulin-like growth factor-1), a hormone that promotes growth and mimics insulin.

The researchers say that their next step will be to study other potential glucagon suppressants, and begin leptin clinical trials within the next year.

ANI