Signs of low-grade systemic inflammation are not uncommon among people who have the pre-diabetic condition known as metabolic syndrome, as well as in animal models of obesity and type 2, or insulin-resistant, diabetes, said senior author H. Henry Dong, Ph.D., assistant professor, Department of Pediatrics, University of Pittsburgh School of Medicine.
"But it's not yet clear if there is a cause-and-effect relationship between chronic exposure to low-grade inflammation and the onset of insulin resistance," he explained. "Other studies have shown that in patients who have inflammation and diabetes, insulin-sensitizing drugs seem to reduce inflammation while anti-inflammatory therapies improve sensitivity to insulin."
Dr. Dong's team examined the role played by a protein called Forkhead Box 01 (Fox01), which his previous research showed contributes to elevations in triglycerides in an animal model of obesity and diabetes.
In the current paper, the researchers found in cultured cells and mouse experiments that Fox01 stimulates inflammatory white blood cells called macrophages, which migrate to the liver and adipose, or fat, tissue in insulin-resistant states, to increase production of a cytokine called interleukin-1 beta (IL-1B). The cytokine in turn interferes with insulin signaling. Insulin typically inhibits Fox01, setting up a feedback loop in healthy tissues that helps regulate insulin levels.
"The findings suggest that when there is a lack of insulin or when cells such as macrophages are resistant to its presence, there are no brakes on Fox01's stimulation of IL-1B and its further interference with insulin signaling," Dr. Dong said. "That might explain why chronic inflammation often is coupled with obesity and type 2 diabetes. Also, a drug that acts on Fox01 might be able to better control blood sugar."
According to the ADA, an estimated 24 million Americans have type 2 diabetes, formerly known as adult-onset diabetes. As obesity becomes more common, however, the prevalence is rising in children. In type 2 diabetes, the body becomes resistant to the effect of insulin, leading to elevated blood sugar levels.
Co- authors of the paper include lead author Dongming Su, M.D., Gina M. Coudriet, Dae Hyun Kim, Ph.D., German Perdermo, Ph.D., Shen Qu, M.D., Sandra Slusher, Hubert M. Tse, Ph.D., Jon Piganelli, Ph.D., and Nick Giannoukakis, Ph.D., all of the Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC and Pitt School of Medicine, and Yi Lu, Ph.D., and Jian Zhang, M.D., Division of Hematology and Oncology, Department of Medicine, Pitt School of Medicine.
The study was funded by the American Diabetes Association and the National Institutes of Health.
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 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. 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.
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy