The brain plays a key role in diminishing type 1 diabetes during leptin therapy, according to new animal study findings by the University of Texas Southwestern Medical Center researchers.
Leptin — a protein hormone produced by the body’s fat cells and key to regulating appetite and metabolism — can reverse life-threatening symptoms in rodents with type 1 diabetes when the hormone is injected under the skin. This is according to past research by Dr. Roger Unger, professor of internal medicine at UT Southwestern.
Until now, the exact mechanism causing these results has remained undetermined.
In the current study, scientists continuously injected leptin into the brains of mice that were unable to produce natural insulin. An inability to produce enough insulin is the key characteristic for type 1 diabetes in humans.
The results showed that introducing leptin into the lateral ventricle of the rodents’ brains actually restored the ill rodents back to good health.
This proves the brain as a potentially crucial site for mediating the metabolism-improving actions of leptin, said Dr. Roberto Coppari, assistant professor of internal medicine at UT Southwestern and senior author of the study involving laboratory mice.
“Our findings really pave the way for understanding the mechanism by which leptin therapy improves type 1 diabetes,” said Coppari.
“Understanding the mechanism is important, because if we can determine how leptin drives these benefits, then we may be able to develop drugs that eliminate the need for insulin.”
The team’s findings also pinpointed the smallest levels of leptin required to maintain the rodents’ food intake, blood sugar levels, and body weight.
A study on human participants is currently under way at UT Southwestern to establish whether adding leptin to regular insulin therapy might help stabilize the up-and-down blood sugar levels of people with type 1 diabetes.
“It might be that leptin treatment is not going to be effective or well-tolerated or that it might cause unwanted effects,” Dr. Coppari said.
“However, if we understand the mechanisms and how leptin improves type 1 diabetes, then perhaps we can develop alternatives to harness those mechanisms.”
Next, Dr. Coppari will study which specific nerve cells in the brain are responsible for the reversal actions of leptin on type 1 diabetes.
“Living without insulin was once considered impossible, but our results have shown that it is possible when leptin receptor signaling in the brain is enhanced,” he added.
“If we can identify which neurons are responsible for driving the anti-type 1 diabetic actions of leptin, we may eventually develop better therapies for individuals with type 1 diabetes.”
The study is found online and will be published in the Proceedings of the National Academy of Sciences.