Featured Research

from universities, journals, and other organizations

Popular diabetes drugs' cardiovascular side effects explained

Date:
May 3, 2011
Source:
Cell Press
Summary:
Drugs known as thiazolidinediones, or TZDs for short, are widely used in diabetes treatment, but they come with a downside. The drugs have effects on the kidneys that lead to fluid retention as the volume of plasma in the bloodstream expands. Now researchers report that those negative consequences arise in more than one way. The findings may lead to the development of improved diabetes therapies.

Drugs known as thiazolidinediones, or TZDs for short, are widely used in diabetes treatment, but they come with a downside. The drugs have effects on the kidneys that lead to fluid retention as the volume of plasma in the bloodstream expands.

"TZDs usually increase body weight by several kilograms," said George Seki of the University of Tokyo. "However, TZDs sometimes cause massive volume expansion, resulting in heart failure."

Now his team reports in the May issue of Cell Metabolism, a Cell Press publication, that those negative consequences arise in more than one way. The findings may lead to the development of improved diabetes therapies.

TZDs act on a hormone receptor known as peroxisome proliferator-activated receptor γ (PPARγ). PPARγ is a master gene of fat cell biology and differentiation, Seki explained, making it an ideal target for diabetes treatment.

However, TZDs also lead to changes in gene expression that enhance the sodium transport system of the kidney and lead to the reabsorption of water and salt, as scientists knew. But, Seki said, that mechanism alone didn't seem to be enough to explain the volume expansion.

Seki's team has found that TZDs also have direct effects on channels in the kidney known as the proximal tubules. TZDs rapidly stimulate sodium-coupled bicarbonate absorption from renal proximal tubules. Inhibitors of PPARγ or other players in the pathway suppress that stimulation, they report.

The researchers confirm that those effects occur regardless of whether PPARγ can bind DNA to influence the activity of other genes.

The discovery helps to explain the speed with which side effects of TZDs can sometimes arise and may lead to strategies to improve insulin resistance without the accompanying severe cardiovascular side effects, the researchers say.

"Massive volume expansion in human subjects usually occurs after weeks of use of TZDs," they wrote. "However, it can also occur as rapidly as 4 days after use of TZDs, supporting the involvement of multiple mechanisms. Thus, combination therapy with different diuretics targeting both renal proximal tubules and the distal nephrons could be a therapeutic option in case of TZD-induced massive volume expansion."

The findings also raise the possibility that other small molecules might bind PPARγ in slightly different ways, leading to different biological responses, they added. In fact, several selective PPARγ modulators have already been developed and appear to induce less fluid retention, at least in animals. Whether that will prove to work in humans to prevent massive fluid retention remains to be seen.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yoko Endo, Masashi Suzuki, Hideomi Yamada, Shoko Horita, Motoei Kunimi, Osamu Yamazaki, Ayumi Shirai, Motonobu Nakamura, Naoyuki Iso-O, Yuehong Li, Masumi Hara, Kazuhisa Tsukamoto, Nobuo Moriyama, Akihiko Kudo, Hayato Kawakami, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Haruki Kume, Yutaka Enomoto, Yukio Homma, George Seki, Toshiro Fujita. Thiazolidinediones Enhance Sodium-Coupled Bicarbonate Absorption from Renal Proximal Tubules via PPARγ-Dependent Nongenomic Signaling. Cell Metabolism, 2011; 13 (5): 550-561 DOI: 10.1016/j.cmet.2011.02.015

Cite This Page:

Cell Press. "Popular diabetes drugs' cardiovascular side effects explained." ScienceDaily. ScienceDaily, 3 May 2011. <www.sciencedaily.com/releases/2011/05/110503132700.htm>.
Cell Press. (2011, May 3). Popular diabetes drugs' cardiovascular side effects explained. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2011/05/110503132700.htm
Cell Press. "Popular diabetes drugs' cardiovascular side effects explained." ScienceDaily. www.sciencedaily.com/releases/2011/05/110503132700.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
CDC Calls for New Ebola Safety Guidelines

CDC Calls for New Ebola Safety Guidelines

AP (Oct. 20, 2014) Centers for Disease Control and Prevention Director Dr. Tom Frieden laid out new guidelines for health care workers when dealing with the deadly Ebola virus including new precautions when taking off personal protective equipment. (Oct. 20) Video provided by AP
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