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!
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences