Featured Research

from universities, journals, and other organizations

How a cancer drug leads to diabetes-like state

Date:
April 3, 2012
Source:
Dana-Farber Cancer Institute
Summary:
Scientists have discovered why diabetic-like symptoms develop in some patients given rapamycin, an immune-suppressant drug that also has shown anti-cancer activity and may even slow aging.

Scientists at Dana-Farber Cancer Institute have discovered why diabetic-like symptoms develop in some patients given rapamycin, an immune-suppressant drug that also has shown anti-cancer activity and may even slow aging.

Related Articles


Rapamycin is widely used to prevent organ rejection and is being tested as a cancer treatment in clinical trials. About 15 percent of patients, however, develop insulin resistance and glucose intolerance after taking the drug; until now, scientists had not identified the reason.

In a study published in Cell Metabolism, the researchers report that normal mice given rapamycin were more likely to have trouble regulating their blood sugar because of a drop in insulin signaling, which in turn was triggered by activity of a protein called Yin Yang 1, or YY1. But animals in which the YY1 protein was "knocked out" in their muscles had no such response to rapamycin -- they were protected against the development of diabetes-like symptoms. This result pinpointed YY1 as the target of rapamycin responsible for the loss of normal insulin function.

One of the finding's implications is that physicians should consider giving anti-diabetes drugs along with rapamycin, says Pere Puigserver, PhD, senior author of the report.

The results also raise a caution flag for researchers and non-scientists who are excited about the potential for rapamycin to extend life, based on recent studies in animals including mammals, he notes.

"The possibility of increased diabetes risk needs to be taken into account" in further research on the anti-aging properties of rapamycin and related compounds, says Puigserver.

Rapamycin is a drug derived from bacteria found on Easter Island, and was approved in 1999 by the FDA as an immunosuppressant in transplant patients.

One of its actions is to inhibit the important mTOR signaling pathway in cells (mTOR stands for "mammalian target of rapamycin"). The mTOR pathway is a critical factor in regulating the growth, proliferation, survival and motility of cells; elevated mTOR activity is a hallmark of many cancers.

In clinical trials rapamycin and a related drug are being evaluated in kidney cancer, brain tumors, and mantle cell lymphoma, among others. Intriguingly, rapamycin has been found in some experiments to extend healthy lifespan in yeast, flies and mammals, and delays age-related diseases, including cancer and atherosclerosis.

But the raised risk of deleterious pre-diabetes symptoms has been a concern and something of a mystery. In 2007, Puigserver and colleagues reported in Nature that mTOR causes an increase in mitochondria -- the cell's power plants -- in skeletal muscles; suppressing mTOR activity with rapamycin led to a diabetic state. That research also revealed that among the proteins "downstream" of mTOR in the signaling pathway is Yin Yang 1 (YY1), a transcription factor -- a protein that controls the expression of genes.

"We thought that maybe YY1 was responsible for the diabetic effects," says Puigserver. An increase in YY1 activity caused by rapamycin could suppress the production of insulin and related hormones which are necessary for muscles to take up glucose (sugar) for energy and keep blood sugar levels stable.

To test that idea, they bred mice that lacked the YYI gene and protein in their skeletal muscles. When these mice were given rapamycin, it didn't affect their muscles' glucose uptake or insulin signaling -- in effect, they were immune to the diabetic effects of rapamycin.

The investigators are continuing their studies: one goal is to discover why only a minority of human patients develop diabetes-like conditions with rapamycin treatment. One possibility that the risk is modulated by dietary factors, Puigserver says.

The first author on the paper is Sharon Blättler, PhD, a postdoc in the Puigserver lab.

The research was supported by grants from the National Institutes of Health and the Muscular Dystrophy Association.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sharon M. Blättler, John T. Cunningham, Francisco Verdeguer, Helen Chim, Wilhelm Haas, Huifei Liu, Klaas Romanino, Markus A. Rüegg, Steven P. Gygi, Yang Shi, Pere Puigserver. Yin Yang 1 Deficiency in Skeletal Muscle Protects against Rapamycin-Induced Diabetic-like Symptoms through Activation of Insulin/IGF Signaling. Cell Metabolism, Volume 15, Issue 4, 4 April 2012, Pages 505-517 DOI: 10.1016/j.cmet.2012.03.008

Cite This Page:

Dana-Farber Cancer Institute. "How a cancer drug leads to diabetes-like state." ScienceDaily. ScienceDaily, 3 April 2012. <www.sciencedaily.com/releases/2012/04/120403124356.htm>.
Dana-Farber Cancer Institute. (2012, April 3). How a cancer drug leads to diabetes-like state. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2012/04/120403124356.htm
Dana-Farber Cancer Institute. "How a cancer drug leads to diabetes-like state." ScienceDaily. www.sciencedaily.com/releases/2012/04/120403124356.htm (accessed October 30, 2014).

Share This



More Health & Medicine News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Reuters - Innovations Video Online (Oct. 29, 2014) — A Swedish amputee who became the first person to ever receive a brain controlled prosthetic arm is able to manipulate and handle delicate objects with an unprecedented level of dexterity. The device is connected directly to his bone, nerves and muscles, giving him the ability to control it with his thoughts. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Google To Use Nanoparticles, Wearables To Detect Disease

Google To Use Nanoparticles, Wearables To Detect Disease

Newsy (Oct. 29, 2014) — Google X wants to improve modern medicine with nanoparticles and a wearable device. It's all an attempt to tackle disease detection and prevention. Video provided by Newsy
Powered by NewsLook.com
Can Drinking Milk Lead To Early Death?

Can Drinking Milk Lead To Early Death?

Newsy (Oct. 29, 2014) — Researchers in Sweden released a study showing heavy milk drinkers face an increased mortality risk from a variety of causes. Video provided by Newsy
Powered by NewsLook.com
Obama: The US Will Not 'run and Hide' From Ebola

Obama: The US Will Not 'run and Hide' From Ebola

AP (Oct. 29, 2014) — Surrounded by health care workers in the White House East Room, President Barack Obama said the U.S. will likely see additional Ebola cases in the weeks ahead. But he said the nation can't seal itself off in the fight against the disease. (Oct. 29) 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