Featured Research

from universities, journals, and other organizations

Study Sheds Light On Why Diabetes Drug Causes Edema

Date:
June 19, 2005
Source:
University of Utah Health Sciences Center
Summary:
In related discoveries with far-reaching implications for treating diabetes and understanding hypertension, University of Utah researchers have learned why thiazolidinediones (TZDs), a major anti-diabetes drug, cause edema and also have found a new pathway critical to fluid metabolism. Identification of this pathway may help understand fundamental mechanisms of blood pressure control.

SALT LAKE CITY -- In related discoveries with far-reaching implications for treating diabetes and understanding hypertension, University of Utah researchers have learned why thiazolidinediones (TZDs), a major anti-diabetes drug, cause edema and also have found a new pathway critical to fluid metabolism. Identification of this pathway may help understand fundamental mechanisms of blood pressure control.

Related Articles


Using knockout-gene technology, the U of U School of Medicine researchers found that when TZD is activating a nuclear receptor, the peroxisome proliferator-activated receptor gamma, in the collecting duct in the kidney, it serves as a mechanism for fluid retention, or edema. The researchers suggest that the distal nephron, for example the collecting duct, is crucial for regulation of sodium balance and blood pressure. The research is published this week in the Proceedings of the National Academy of Sciences online.

The discoveries may point the way to developing different drugs to treat Type II diabetes and open an entirely new area in the study of hypertension, according to Tianxin Yang, M.D., Ph.D., the two-year study's principal investigator, associate professor of internal medicine at the U medical school, and staff physician at the George E. Wahler Veterans Affairs Medical Center in Salt Lake City.

An estimated 18 million Americans suffer from diabetes. TZD compounds have been shown to be highly effective in lowering blood glucose and lipid levels and in controlling blood pressure.

"It's almost a perfect drug for diabetes," Yang said.

But many diabetics who use TZD eventually have to discontinue the drug because it causes edema. About 1 percent of people who take TZD get pulmonary edema and chronic heart failure, both being potentially life-threatening conditions.

TZD works by activating PPAR-gamma, a receptor that helps sensitize the body to insulin. PPAR is found in muscle, fat, kidney, and heart and controls fatty acid and lipid metabolism. In the kidney, PPAR is found in the collecting duct, a critical site for the control of fluid metabolism.

To test the role of PPAR in edema, Yang created mice that specifically lacked PPAR-gamma in the collecting duct. He then administered TZD to these mice, as well as to a control group that didn't lack PPAR-gamma.

The mice not lacking PPAR-gamma showed about a 10 percent average increase in body weight because of fluid retention. The blood plasma volume of these mice increased by one-third, Yang said. But the mice bred without PPAR-gamma experienced no increase in body weight in response to the drug, according to Yang.

"This tells us that the body weight gain is regulated by PPAR-gamma in the collecting duct," he said. "We also found this drug decreased the sodium excretion in urine, so this could explain the fluid retention."

The mice without PPAR in the collecting ducts incurred no changes in sodium reabsorption, while those with PPAR excreted less sodium through urination. Yang said that the distal nephron, which is usually subject to hormone regulation in the kidney, serves as a key pathway for keeping an accurate amount of sodium in the body.

Hypertension affects one in four U.S. adults and long had been considered a cardiovascular disease. But research now also focuses on the kidneys and the role of the distal nephron in retaining sodium opens a new area for study, he said.



Story Source:

The above story is based on materials provided by University of Utah Health Sciences Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Utah Health Sciences Center. "Study Sheds Light On Why Diabetes Drug Causes Edema." ScienceDaily. ScienceDaily, 19 June 2005. <www.sciencedaily.com/releases/2005/06/050619081825.htm>.
University of Utah Health Sciences Center. (2005, June 19). Study Sheds Light On Why Diabetes Drug Causes Edema. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2005/06/050619081825.htm
University of Utah Health Sciences Center. "Study Sheds Light On Why Diabetes Drug Causes Edema." ScienceDaily. www.sciencedaily.com/releases/2005/06/050619081825.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com
Ebola: Life Without School in Guinea

Ebola: Life Without School in Guinea

AFP (Nov. 21, 2014) Following the closure of schools and universities in Guinea because of the Ebola virus, students look for temporary work or gather in makeshift classrooms to catch up on their syllabus. Duration: 02:14 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins