UF study shows leptin could combat type 2 diabetes
|By April Frawley Birdwell
GAINESVILLE, Fla. - 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.
Aside from keeping blood sugar and insulin levels down, the rodents that received gene therapy also lived longer than obese rodents that did not, Kalra said.
"Currently we do not know if that is due to the correction of the diabetes or many of the diseases associated with diabetes," Kalra said. "It is clinically known that diabetic patients have early onset mortality. If the diabetes is managed, there is an improvement in lifespan."
Martin G. Myers, M.D., Ph.D., an associate professor of medicine and physiology at the University of Michigan Medical School who also studies leptin, said other studies in recent years have shown similar findings, albeit without the use of gene therapy.
"Most of what is in this paper is not surprising," Myers said.
While he noted that it was good to see the leptin was still working in the rodents for the full 15 weeks that UF researchers were conducting the study, Myers said it is unlikely that doctors will employ leptin gene therapy in humans.
Gene therapy would be an ideal treatment because it just takes one shot, Kalra said, adding it is also likely drugs could be developed to simulate leptin's action in a pill form, which is easier to give to patients.
"What we have shown in animals is very effective," Kalra said. "It can be done."
Boy undergoes rare surgery to correct life-threatening disease
By April Frawley Birdwell
GAINESVILLE, Fla. - A 4-year-old Ocala boy born with a severe form of scoliosis became one of the first children in the Southeast to receive a titanium rib device that will allow his rib cage to expand as he grows, said University of Florida surgeons, who performed the two-and-a-half-hour operation today (September 29) at Shands at UF medical center.
The device spreads vertically to expand his chest cavity, creating more room for his organs while correcting his scoliosis, a curvature of the spine. Unlike adolescents who develop scoliosis, children born with the disease usually have ribs that have fused, preventing their chest cavities from growing even as the organs inside them continue to enlarge, said UF pediatric orthopaedic surgeon Raymund Woo, M.D., who led the procedure. Woo is an associate professor of orthopaedic surgery and chief of pediatric orthopaedics at UF's College of Medicine.
Prior to the development of the titanium rib, a thin bar that can be manually adjusted so the rib cage can expand over time, many children with severe congenital scoliosis died as their bodies outgrew their fused ribs, Woo said. Fusing rods into the spine, the standard surgery to treat the disease in teens and adults, is not considered an option for small children: Although it would straighten their spines, it would not solve the problem of multiple fused ribs, Woo said.
"They don't have enough room in their rib cages for their organs to grow," he said. "(Without that) these kids are doomed to die. This is really a major step forward in the treatment of this disease."
Only about 1,000 children in the United States have this severe form of congenital scoliosis with fused ribs, Woo said. The main problem these children face is that their fused ribs constrict lung development, said George H. Thompson, a professor of orthopaedics and director of pediatric orthopaedics at Case Western Reserve University. This makes the titanium rib's ability to expand the chest cavity particularly important, he said.
"The lung really gets most of its development in the first eight years of life," said Thompson, also president of the Scoliosis Research Society.
Shamar Honor, who has been Woo's patient since he was about 6 months old, received two of the titanium ribs. Woo had to separate some of the fused ribs so they could be attached to his rib cage. The only parts of the vertical ribs that actually touch the boy's bones are the points where they are attached, Woo said.
Shamar was listed in good condition after the surgery, Woo said. Woo will not know how well the device works until Shamar's scoliosis worsens or improves, he said.
The titanium ribs have additional length inside of them, which will allow Woo to expand them by making small incisions over the spots where the device is attached to Shamar's rib. He will have to come back every six months to have them adjusted.
"I thought it was good news," said Robbietta Honor, Shamar's mother, recalling the day when Woo told her about the surgery. "I can notice it more as he gets older, one side is growing and the other side isn't. He's lopsided."
Because the surgery is so unusual, Woo and UF pediatric surgeon David Kays, M.D., both received special training to learn how to perform it. Kays assisted in the surgery and Vincent Deeney, M.D., an orthopaedic surgeon from the University of Pittsburgh who has performed the surgery before, was in the room to offer guidance. Another team was also in place to monitor Shamar's spinal cord, Woo said.
The U.S. Food and Drug Administration approved the device, produced by the Paoli, Pa., company Synthes, for humanitarian use in 2004. According to the FDA, the humanitarian use exemption was put in place to encourage companies to develop devices and treatments for conditions that affect fewer than 4,000 people. Fewer cases can dissuade some companies from sinking research dollars into a device because fewer patients sometimes equate to less profit, Woo said.
Aside from correcting scoliosis and allowing the rib cage to expand, the device will also allow Shamar to maintain flexibility, something that older scoliosis patients typically sacrifice when rods are fused into their spines.
"This allows you to have the best of both worlds," Woo said.