The discovery by researchers in Hopkins' Institute of Basic Biomedical Sciences and McKusick-Nathans Institute for Genetic Medicine reveals that a protein called GCN5 is critical for controlling a domino-like cascade of molecular events that lead to the release of sugar from liver cells into the bloodstream. Understanding the role of GCN5 in maintaining blood sugar levels is leading to a clearer picture of how the body uses sugar and other nutrients to make, store and spend energy.
"Understanding the ways that energy production and use are controlled is crucial to developing new drugs and therapies," says the report's senior author, Pere Puigserver, Ph.D., an assistant professor of cell biology at Hopkins.
The inability to properly regulate blood sugar levels leads to conditions like obesity and diabetes. Both type 1 and type 2 diabetes cause blood sugar levels to stay too high, which can lead to complications like blindness, kidney failure and nerve damage.
"Diabetes is a really big problem, even when patients are given insulin and stay on strict diets," says Carles Lerin, Ph.D., a postdoctoral fellow in cell biology at Hopkins and an author of the report. "In the absence of a cure for the disease, we are really trying to focus on finding better treatment because currently available methods just don't work that efficiently," he says.
The body keeps blood sugar – known as glucose – within a narrow range. Extra glucose floating through the bloodstream, which is common after eating a meal, is captured and kept in the liver. When blood glucose runs low, the liver releases its stores back into the bloodstream. When those reserves are tapped out, liver cells turn on genes to make more glucose to fuel the body.
The research team found that GCN5 chemically alters another protein called PGC-1alpha that normally turns on a set of genes to manufacture enzymes required for glucose release. When GCN5 is fully functional in liver cells, this cascade is turned off and glucose is not released from those cells. Removal of functional GCN5 from liver cells restores the cells' ability to release glucose.
The researchers showed that GCN5 alters its target, sabotaging it by adding a chemical tag called an acetyl group. By using molecules that glow fluorescently, the researchers saw under high-power microscopes that GCN5 carries its tagged target to a different location in the cell's nucleus – sequestering it away from the genes it's normally meant to turn on.
"GCN5 has been generally shown to turn on genes. No one knew that GCN5 could be used to turn off pathways" says Lerin. "It was a bit of a surprise."
When the researchers put GCN5 into live mice, they found that it can in fact decrease blood glucose levels. Liver cells in mice that were given no food for 16 hours actively release glucose into the bloodstream. Introducing GCN5 into their livers, however, causes blood glucose levels in these mice to be reduced.
"These results show that changing GCN5 is sufficient to control the sugar balance in mice," says Puigserver. "Therefore, GCN5 has the potential to be a target for therapeutic drug design in the future."
Audrey Huang | EurekAlert!
Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg
New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences