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!
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy