July 30, 2004

Lizard spit may treat diabetes

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The saliva of Gila monsters may hold the treatment for type 2 diabetes. /Courtesy Nashville Zoo

Lizard spit may treat diabetes

The saliva of a venomous lizard may hold treatment for those with type 2 diabetes.

Diabetes researchers at Vanderbilt University Medical Center are testing a new drug, which is derived from the saliva of the Gila monster.

This study is one of many novel research projects under way by researchers at the Vanderbilt Diabetes Center.

In other clinical trials, a new drug, called Exenatide, has produced significant results in reducing blood glucose levels in type 2 diabetics. In these studies Exenatide has not only lowered blood glucose levels, but also has shown an ability to reduce the body weight of study participants.

“Treatment of type 2 diabetes has become very complicated over the last 10 years because we understand the things that go wrong in the body causing type 2 diabetes are themselves complicated,” said Stephen Davis, M.D., the Rudolph H. Kampmeier Professor of Medicine and chief of the Division of Diabetes, Endocrinology and Metabolism.

Davis says the body of a person with type 2 diabetes no longer makes enough insulin, and the insulin that’s produced by the body doesn’t work effectively. Also, people with type 2 diabetes have increased production of a hormone called glucagon. This hormone counteracts the effect of insulin. The tipping point for many people with type 2 diabetes is brought about by an expanding waistline.

Hormonal imbalance, and a lack of sufficient insulin production, causes an increase in the appetite of those with diabetes that proves very difficult to control.

The way diabetes treatment has evolved is by trying to attack all these complications with different combinations of oral and injected medications.

“The great excitement about this new treatment is that it can attack all these problems in one go,” Davis said.

The new treatment known to researchers as a glucagon-like peptide-1 analog, or GLP-1, is a naturally occurring hormone in the human GI tract. GLP-1’s property is to increase insulin when glucose is high, and shut off production of the anti-insulin hormone glucagon. GLP-1 slows down the stomach’s emptying of glucose, and can decrease appetite, which results in weight loss.

The problem in humans is that these hormones only last about two minutes in the bloodstream. The body produces an enzyme that rapidly inactivates them. Now this naturally occurring hormone has been modified to overcome the effect of the enzyme and last much longer in the body.

“The new agent we’re studying actually comes from the saliva of the Gila monster and is called Exendin-4,” Davis said. “This substance from the Gila monster is about 50 percent identical to human GLP-1, but doesn’t get attacked by the enzyme in the bloodstream, and therefore is not rapidly inactivated.”

Many people with type 2 diabetes must take multiple injections of insulin throughout each day to control blood-glucose levels. Davis says one injection of Exendin-4 can last up to 12 hours.

Exendin-4 has already successfully undergone several smaller trials, and three large FDA registration trials.

“The early results of these trials look very promising,” he said. “The agent can lower blood-glucose, lower the three-month measurement (knowns as A1c) of blood-glucose control, lower weight by about four to seven pounds, and by itself does not cause hypoglycemia (low blood sugar).”

VUMC’s study is a new study examining how Exendin-4 can be used in combination with other anti-diabetes medications for the control of day-to-day blood glucose levels in those with type 2 diabetes.

“We are also carefully examining whether Exendin-4 can have an effect in stimulating the body’s production of insulin,” he said. “This is a very important part of our study. At the moment, continuing loss of insulin secretion cannot be stopped in type 2 diabetics.” VUMC’s study is also closely monitoring the effects of Exendin-4 on participants’ body weight and appetite.

“My expectation is that these GLP-1-like compounds are going to be the next big breakthrough in the treatment of diabetes, and we at Vanderbilt want to be at the forefront of diabetes clinical research and care. We welcome the opportunity to look at these new compounds,” Davis said.

Participants, ages 35 to 70, with type 2 diabetes are still needed for the Exendin-4 trial. Potential candidates need to be on both insulin and oral medications to control their disease. For more information about the Exendin-4 study, or other diabetes studies, please contact the Vanderbilt Diabetes Center at 936-1824.

by John Howser

Vanderbilt’s division of Diabetes, Endocrinology and Metabolism is hosting its second annual “Diabetes In Motion,” event, a comprehensive educational event that is free and open to the public, on Saturday, Aug. 7, from 8:30 a.m. until 3:30 p.m. at Blair Ingram Hall.

The event is a comprehensive one-day program to motivate individuals with diabetes to put “Diabetes In Motion” to manage their disease more effectively with physical activity. The event offers a health fair, panel discussions with diabetes experts, and diabetes workshops.

Participants are encouraged to come out for an early bird walk from 7:15 – 8 a.m., led by Robert Sweetgall, nationally known as “The Walking Expert.” Sweetgall has walked across America seven times, and is the author or co-author of 17 books on walking.

“Unfortunately, physical activity has become a low priority for peoples’ schedules because they’re so busy. They just don’t have time to exercise,” said Stephen Davis, M.D., Ph.D., chief of the division of Diabetes, Endocrinology and Metabolism.

“There are so many other things competing for people’s interests. We want to show them there are ways to incorporate physical activity into their daily routine. Exercise is one of the four cornerstones in the management of diabetes.”

Exercise has been proven to reduce the risk of developing diabetes and other health problems such as coronary artery disease, high blood pressure, and some types of cancer. Yet more than 60 percent of U.S. adults do not get the recommended amount of exercise.

“Our goal is to provide an educational and fun forum to learn about exercise,” Davis said. “As it turns out, any form of physical activity is useful. It doesn’t have to be in long bursts. The cumulative effects are important.”

“Diabetes In Motion” will offer opportunities to learn how to incorporate exercise into a daily routine. The event will include topics presented by a diverse group of experts — physicians, Ph.D. level researchers, exercise physiologists, nutritionists, nurse practitioners, and Sweetgall.

The event offers free admission, resources and information, along with a free lunch and other refreshments.

Blair Ingram Hall is located on Vanderbilt’s campus at the corner of 24th Avenue South and Children’s Way. Free event parking is available just across the street from Blair Ingram Hall in the South Garage (formerly known as Capers Garage) next to Children’s Hospital.

To register for “Diabetes In Motion” please call (615) 343-6000.