Featured Research

from universities, journals, and other organizations

Diabetes drug side effects traced to fat action

Date:
July 7, 2011
Source:
Cell Press
Summary:
For better or worse, a popular class of anti-diabetic drugs does more than lower blood sugar. One known as rosiglitazone (trade name Avandia) has been in the spotlight for its possible link to increased cardiovascular events, but it also seems to come with unexplained vascular benefits and an unwelcome tendency for weight gain. Now, two separate studies explore those other effects of the drugs known collectively as thiazolidinediones (TZDs), both of which stem from their activity in fat.

For better or worse, a popular class of anti-diabetic drugs does more than lower blood sugar. One known as rosiglitazone (trade name Avandia) has been in the spotlight for its possible link to increased cardiovascular events, but it also seems to come with unexplained vascular benefits and an unwelcome tendency for weight gain. Now, two separate studies in the July Cell Metabolism, explore those other effects of the drugs known collectively as thiazolidinediones (TZDs), both of which stem from their activity in fat.

The findings offer new biological insights into fat tissue and its role as a central component of metabolic control. They may also pave the way for the development of new and better drugs, according to the researchers.

"TZDs have lots of side effects," said Jonathan Graff of the University of Texas Southwestern Medical Center. "We may find ways to replace them with drugs that have fewer."

Earlier studies showed that TZDs remodel fat (adipose) tissue and that they lead to the recruitment of new fat cells known as adipocytes. "TZDs alter adipose tissue to make you fatter," Graff said.

His team wanted to know whether those effects could be traced to adipose stem cells as the source of all those new adipocytes. Adipose stem cells were earlier identified in the walls of the blood vessels that feed adipose tissue, suggesting they might be an accessible target for therapies.

Indeed, they show in mice that rosiglitazone markedly increases the evolution of adipose stem cells into new adipocytes, perhaps explaining why those taking the drugs tend to put on pounds. After two months on the drug, however, the animals' stem cells were "profoundly altered" both molecularly and functionally. At that point, "they don't proliferate in the same way and they no longer form fat cells," Graff said. It was as if the fat cell progenitors had worked overtime and were spent.

The findings offer important evidence that the biology of fat might be altered for therapeutic ends via stem cells, the researchers say. They also provide important new insight into how TZDs work and how they might be improved.

"Although TZDs are effective at lowering blood glucose levels, side effects and concerns that TZDs increase cardiovascular risk have hastened the need to find alternative therapeutics," Graff's team wrote. "A better understanding of whether and how TZDs modulate the adipose lineage may shed light on their insulin-sensitizing efficacy, and may also help to develop the next generation insulin-sensitizers."

In the second study, Yu Huang of Chinese University of Hong Kong and Aimin Xu of the University of Hong Kong tested whether the vascular benefits of rosiglitazone could be connected to the fat-derived hormone adiponectin. Adiponectin is unusual among fat hormones in that its levels generally decline in those who are obese and many earlier studies by Huang and Xu's team and others suggested it might have a protective effect on blood vessels.

In diabetic mice, the researchers found that adiponectin is required for the vascular benefits of treatment with rosiglitazone. Rosiglitazone treatment also stimulated the release of adiponectin from isolated fat tissue, and fat tissue transplanted from treated mice relaxed the blood vessels of untreated diabetic mice.

" Our study emphasizes the importance of adipose tissue-derived adiponectin in response to TZD," Huang said. "This suggests that development of pharmacological agents that can elevate adiponectin, but avoid the undesirable effects of TZDs, may represent an effective therapeutic approach for treating or preventing vascular diseases induced by obesity and diabetes."

He says they have also identified several natural compounds in edible herbs that boost adiponectin levels by other means. They plan to test whether those compounds might have therapeutic use.


Story Source:

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


Journal References:

  1. Wing Tak Wong, Xiao Yu Tian, Aimin Xu, Jun Yu, Chi Wai Lau, Ruby L.C. Hoo, Yu Wang, Vivian W.Y. Lee, Karen S.L. Lam, Paul M. Vanhoutte et al. Adiponectin Is Required for PPARγ-Mediated Improvement of Endothelial Function in Diabetic Mice. Cell Metabolism, 6 July 2011; 14(1) pp. 104 - 115 DOI: 10.1016/j.cmet.2011.05.009
  2. Wei Tang, Daniel Zeve, Jin Seo, A-Young Jo, Jonathan M. Graff. Thiazolidinediones Regulate Adipose Lineage Dynamics. Cell Metabolism, 6 July 2011; 14(1) pp. 116 - 122 DOI: 10.1016/j.cmet.2011.05.012

Cite This Page:

Cell Press. "Diabetes drug side effects traced to fat action." ScienceDaily. ScienceDaily, 7 July 2011. <www.sciencedaily.com/releases/2011/07/110705123342.htm>.
Cell Press. (2011, July 7). Diabetes drug side effects traced to fat action. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2011/07/110705123342.htm
Cell Press. "Diabetes drug side effects traced to fat action." ScienceDaily. www.sciencedaily.com/releases/2011/07/110705123342.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) 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:
from the past week

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