Pilot studies, published online April 22 in Diabetes, show the enzyme O-GlcNAcase is up to two to three times higher in people with diabetes and prediabetes than in those with no disease: “That’s a big difference, especially in an enzyme that’s as tightly regulated as this one is,” says Gerald Hart, Ph.D., the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine.
Building on their previous research, which showed how an abundant but difficult-to-detect sugar switch known as O-GlcNAc (pronounced oh-GLICK-nack) responded to nutrients and stress, the Hopkins team knew this small molecule was elevated in the red cells of patients with diabetes. “The question was whether the elevation happened in the earliest stages of diabetes and therefore might have value as a diagnostic tool,” Hart said.
To find out, Kyoungsook Park, a graduate student of biological chemistry working in Hart’s lab, focused on levels of O-GlcNAcase, an enzyme that removes O-GlcNAc in red cells. O-GlcNAc modifies many of the cell’s proteins to control their functions in response to nutrients and stress. Nutrients, such as glucose and lipids, increase the extent of O-GlcNAc modification of proteins affecting their activities. When the extent of O-GlcNAc attached to proteins becomes too high, as occurs in diabetes, it is harmful to the cell.
First, Park purified human red blood cells by depleting them of their main constituent, hemoglobin. The samples had been collected by two sources — the National Institute of Diabetes, Digestive and Kidney Diseases, or NIDDK, and Johns Hopkins Diabetes Center in collaboration with Christopher D. Saudek, M.D. — and characterized as normal (36 samples), prediabetes (13 samples) and type 2 diabetes (53 samples) according to traditional tests that require patient fasting. Defined as normal hemoglobin A1c with impaired fasting glucose, prediabetes is an intermediate state of altered glucose metabolism with a heightened risk of developing type 2 diabetes and other associated complications.
Then, she measured and compared the amount of the enzyme protein within the red cells associated with the sugar molecule, O-GlcNAc.“When I checked the enzyme levels and saw how dramatically different they were between the prediabetic cells and the controls, I thought I did something wrong,” Park says. “I repeated the test five times until I could believe it myself.”
“This is an example of how basic research is directly affecting a serious disease,” Hart says, adding that his team’s pilot studies encourage further investigation of a method that potentially could fill the void that currently exists for an easy, accurate routine test for prediabetes. “Only a much larger clinical trial will determine if, by measuring O-GlcNAcase, we can accurately diagnose prediabetes.”
In addition to Park and Hart, Chistopher D. Saudek, also of Johns Hopkins University School of Medicine, is an author of the paper.
Funding was provided by the NIH NIDDK.
On the Web:
Hart lab: http://biolchem.bs.jhmi.edu/pages/facultydetail.aspx?AspXPage=g_A13E315C00C04DFD949FD3E57BA45181:ID%3D83
Johns Hopkins Comprehensive Diabetes Center: http://www.hopkinsmedicine.org/diabetes/Media Contacts:
Maryalice Yakutchik | EurekAlert!
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology