Usually, the liver stores excess blood sugar as glycogen, which it doles out overnight during sleep and other periods of fasting to keep glucose levels within a normal physiological range, explained H. Henry Dong, Ph.D., associate professor of pediatrics, Pitt School of Medicine. But in diabetes, the liver continues to pump out glucose even when insulin is provided as a treatment.
"Scientists have been trying to find the factors that contribute to this liver overproduction of glucose for decades," Dr. Dong said. "If we can control that pathway, we should be able to help reduce the abnormally high blood sugar levels seen in patients with diabetes."
He and his team have been studying a family of proteins called Forkhead box or FOX, and for the current project focused on one called FOX06. They found that mice engineered to make too much FOX06 developed signs of metabolic syndrome, the precursor to diabetes, including high blood sugar and high insulin levels during fasting as well as impaired glucose tolerance, while mice that made too little FOX06 had abnormally low blood sugars during fasting.
"In a normal animal, a glucose injection causes blood sugar level to rise initially and then it goes back to normal range within two hours," Dr. Dong said. "In animals that made too much FOX06, blood sugar after a glucose injection doesn't normalize within two hours. They have lost the ability to regulate the level while the liver keeps making unneeded glucose."
Other experiments showed that diabetic mice have abnormally high levels of FOX06 in the liver, he added. Blocking the protein markedly reduced liver production of glucose, although blood sugar did not completely normalize. Within two weeks of treatment, there was significant improvement in blood sugar and glucose metabolism in diabetic mice.
Tests with human liver cells echoed the importance of FOX06's role in glucose production.
"These findings strongly suggest that FOX06 has potential to be developed as a therapeutic target," Dr. Dong said. "If we can inhibit its activity, we can possibly slow the liver's production of glucose in patients with diabetes and better control blood sugar levels."
Co-authors include lead author Dae Hyun Kim, Ph.D., and other researchers from the University of Pittsburgh's departments of Pediatrics and of Pathology. The study was funded by the National Institutes of Health.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.
About Children's Hospital of Pittsburgh of UPMC
Renowned for its outstanding clinical services, research programs and medical education, Children's Hospital of Pittsburgh of UPMC has helped establish the standards of excellence in pediatric care. From Ambulatory Care to Transplantation and Cardiac Care, talented and committed pediatric experts care for infants, children and adolescents who make more than 1,000,000 visits to Children's, its many neighborhood locations, and Children's Community Pediatrics practices each year.
Children's also consistently has been named to several elite lists of pediatric health care facilities, including U.S. News & World Report's Honor Roll of America's "Best Children's Hsopitals" and the Leapfrog Group. Also, Pediatric research programs at Children's Hospital and the University of Pittsburgh School of Medicine ranked eighth in number of grants from the NIH for fiscal year 2010.
Anita Srikameswaran | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering