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

November 30, 2010, Baylor College of Medicine

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 ," 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 ."

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 goes up and down as the body needs.

More information:

Related Stories

Recommended for you

Scientists produce human intestinal lining that re-creates living tissue inside organ-chip

February 16, 2018
Investigators have demonstrated how cells of a human intestinal lining created outside an individual's body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing ...

Data wave hits health care

February 16, 2018
Technology used by Facebook, Google and Amazon to turn spoken language into text, recognize faces and target advertising could help doctors fight one of the deadliest infections in American hospitals.

Researcher explains how statistics, neuroscience improve anesthesiology

February 16, 2018
It's intuitive that anesthesia operates in the brain, but the standard protocol among anesthesiologists when monitoring and dosing patients during surgery is to rely on indirect signs of arousal like movement, and changes ...

Team reports progress in pursuit of sickle cell cure

February 16, 2018
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, according to Rice University bioengineer Gang Bao.

Appetite-controlling molecule could prevent 'rebound' weight gain after dieting

February 15, 2018
Scientists have revealed how mice control their appetite when under stress such as cold temperatures and starvation, according to a new study by Monash University and St Vincent's Institute in Melbourne. The results shed ...

First study of radiation exposure in human gut Organ Chip device offers hope for better radioprotective drugs

February 14, 2018
Chernobyl. Three Mile Island. Fukushima. Accidents at nuclear power plants can potentially cause massive destruction and expose workers and civilians to dangerous levels of radiation that lead to cancerous genetic mutations ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.