From Deseret News archives:
U. hopeful on diabetes-linked study
The team may have found why TZD causes edema
Dr. Tianxin Yang, the two-year study's principal investigator and associate professor of internal medicine in the U. medical school, said TZD is the most effective antidiabetes drug.
"It's a very important, very critical drug, but a major struggle with the drug is edema," Yang said.
The average person taking TZD gains 1.5 to 6 kilograms, Yang said. But some patients have gained more than 20 kilograms.
Many researchers have suggested the edema is caused by the heart, brain, blood vessels or intestinal tract. But Yang said he thinks the edema is coming from the kidney.
The U. researchers studied a nuclear receptor, the peroxisome proliferator-activated receptor (PPAR) gamma, in a special section of the kidney to determine if that was causing fluid retention.
"Body fluid has to be tightly controlled," Yang said. "The kidney's major function is to control fluids."
The researchers used knockout gene technology to remove the PPAR-gamma from the kidneys of several mice. Then they gave the mice TZD and found that the mice didn't experience any body weight gain. They also didn't experience an increase in plasma volume.
The researchers gave TZD to a control group of mice that still had the PPAR-gamma, and after nine days the mice experienced a body weight increase of approximately 10 percent.
"When we gave this drug to the control animals, we found exactly what happened in humans — they gained body weight," Yang said.
That suggests the kidney is solely responsible for the weight gain.
The PPAR-gamma receptors are also found in several places in the body, including muscles, fat, heart, brain tissue and the gastrointestinal tract. When patients use TZD, the receptors in the muscles and fats help stimulate insulin.
Yang said if researchers could develop a new drug that activated the receptors in the muscles and fat but not in the kidney, that would be an ideal drug. Yang said he may collaborate with the company that makes TZD to help develop a better drug.
"We feel this is a breakthrough," Yang said. "We understand the mechanism by which this causes the increase of body weight."
E-mail: nclemens@desnews.com
