Featured Research

from universities, journals, and other organizations

SRC-1 controls liver's 'sweet spot' for glucose production

Date:
November 30, 2010
Source:
Baylor College of Medicine
Summary:
SRC-1 (steroid receptor coactivator) orchestrates glucose production in the liver, regulating the activity of a cascade of enzymes that turns sugar production on and off in the liver, according to new research.

SRC-1 (steroid receptor coactivator) orchestrates glucose production in the liver, regulating the activity of a cascade of enzymes that turns sugar production on and off in the liver, said Baylor College of Medicine and Duke University Medical Center researchers in a report that appears in the current issue of Cell Metabolism.

"As we achieve a better understanding of gluconeogenesis (production of glucose) in the liver, we can look for new ways to treat metabolic diseases such as type 2 diabetes," said Dr. Jean-Francois Louet, instructor in molecular and cellular biology at BCM and a first author of the report. Dr. Atul R. Chopra, a resident physician at BCM, is the other first author.

SRC-1 is a member of a family of steroid receptor coactivators that control important processes in the body. Dr. Bert O'Malley, chair of molecular and cellular biology at BCM and a senior author of the report, discovered SRC-1 and has been a pioneer in uncovering the role of these molecules as cellular master regulators.

"For some years, cell and animal studies have indicated a 'missing control protein' in gluconeogenesis," said O'Malley. "In this study, we identify SRC-1 as this missing factor. Our identification of the coactivator SRC-1 as a 'master actor' in this tight control provides a possible therapeutic target for regulating liver glucose production."

The liver plays an important role in gluconeogenesis -- the production of glucose (from non-sugar source) in response to need, as when you fast. It keeps glucose levels in balance -- increasing the levels when needed and turning off that "spigot" when you eat and the levels of glucose increase.

"Ninety percent of endogenous (within the body) glucose production is in the liver," said Louet. He and his colleagues showed that mice that lack SRC-1 have hypoglycemia (too little sugar in their blood) when they have just eaten and when they are fasting.

"Without SRC-1, glucose production is impaired in the animals," he said. When he and his colleagues restored the SRC-1 to the liver tissues in the animal, glucose levels in the blood became normal.

In collaboration with members of the laboratory of Dr. Christopher B. Newgard (another senior author of the report) at Duke, the team used metabolomics to see what was happening in the tissue and blood from the mice that lacked SRC-1. Metabolomics is the study of a complete collection of metabolites present in a cell or tissue under a particular set of conditions. The collection is called the metabolome.

"We found something we had never seen before. There was strong disorganization of the production of some metabolites that are important for regulating gluconeogenesis," said Louet.

As the group collaborated, it found that SRC-1 controls a gene for a transcription factor called C/EBP alpha that in turn targets a gene for an enzyme called pyruvate carboxylase, which is crucial to beginning the process of gluconeogenesis. (A transcription factor regulates the copying of specific genes [DNA] into a form of RNA the cell's machinery uses to build a protein.) Mice born lacking C/EBP alpha die soon after birth, an indication of the importance of this gene.

SRC-1 keeps these genes in tight control, insuring that the production of glucose in the liver goes up and down as the body needs.

Others who took part in this research include Jorn V. Sagen, Brian York, Mounia Tannour-Louet, Pradip K. Saha, Suoling Zhou, Franco DeMayo and Jianming Xu of BCM, and Jie An, Robert D. Stevens, Brett R. Wenne, Olga R. Ilkayeva and James R. Bain of Duke. O'Malley is the Thomas C. Thompson Professor of Molecular and Cellular Biology at BCM.

Funding for this work came from the National Institutes of the Health, the Norwegian Cancer Society, the University of Bergen and the Norwegian Society of Endocrinology


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jean-Francois Louet, Atul R. Chopra, Jorn V. Sagen, Jie An, Brian York, Mounia Tannour-Louet, Pradip K. Saha, Robert D. Stevens, Brett R. Wenner, Olga R. Ilkayeva et al. The Coactivator SRC-1 Is an Essential Coordinator of Hepatic Glucose Production. Cell Metabolism, Volume 12, Issue 6, 606-618, 1 December 2010 DOI: 10.1016/j.cmet.2010.11.009

Cite This Page:

Baylor College of Medicine. "SRC-1 controls liver's 'sweet spot' for glucose production." ScienceDaily. ScienceDaily, 30 November 2010. <www.sciencedaily.com/releases/2010/11/101130122031.htm>.
Baylor College of Medicine. (2010, November 30). SRC-1 controls liver's 'sweet spot' for glucose production. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2010/11/101130122031.htm
Baylor College of Medicine. "SRC-1 controls liver's 'sweet spot' for glucose production." ScienceDaily. www.sciencedaily.com/releases/2010/11/101130122031.htm (accessed August 28, 2014).

Share This




More Health & Medicine News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mini Pacemaker Has No Wires

Mini Pacemaker Has No Wires

Ivanhoe (Aug. 27, 2014) Cardiac experts are testing a new experimental device designed to eliminate major surgery and still keep the heart on track. Video provided by Ivanhoe
Powered by NewsLook.com
After Cancer: Rebuilding Breasts With Fat

After Cancer: Rebuilding Breasts With Fat

Ivanhoe (Aug. 27, 2014) More than 269 million women are diagnosed with breast cancer each year. Many of them will need surgery and radiation, but there’s a new simple way to reconstruct tissue using a patient’s own fat. Video provided by Ivanhoe
Powered by NewsLook.com
Blood Clots in Kids

Blood Clots in Kids

Ivanhoe (Aug. 27, 2014) Every year, up to 200,000 Americans die from a blood clot that travels to their lungs. You’ve heard about clots in adults, but new research shows kids can get them too. Video provided by Ivanhoe
Powered by NewsLook.com
Radio Waves Knock out Knee Pain

Radio Waves Knock out Knee Pain

Ivanhoe (Aug. 27, 2014) Doctors have used radio frequency ablation or RFA to reduce neck and back pain for years. But now, that same technique is providing longer-term relief for patients with severe knee pain. Video provided by Ivanhoe
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