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Hopkins team discovers sweet way to detect prediabetes
Date:7/8/2010

Having discovered a dramatic increase of an easy-to-detect enzyme in the red blood cells of people with diabetes and prediabetes, Johns Hopkins scientists say the discovery could lead to a simple, routine test for detecting the subtle onset of the disease, before symptoms or complications occur and in time to reverse its course.

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 C
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Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

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