Thursday, July 8, 2010

HOPKINS TEAM DISCOVERS SWEET WAY TO DETECT PREDIABETES

July 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 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.”

Hart speculates that in diabetes and prediabetes, it’s not a good thing for the increased amount of sugar to be attached to proteins, so the cell is responding by elevating the enzyme that gets rid of it.

“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.


New research explains how galaxy centers light up

Galaxies like our own were built billions of years ago from a deluge of giant clouds of gas, some of which continue to rain down. Now new calculations tie the rain of giant clouds of gas to active galactic nuclei (AGN), the extremely bright centers of some galaxies. If a gas cloud with millions of times more mass than our Sun wanders too close to the center of a galaxy, it can either be consumed by the supermassive black hole that lurks there or, through shocks and collapse, give birth to new stars.

"For a while, people have known that gas clouds are falling onto galaxies, and they've also known that active galactic nuclei are powered by gas falling onto supermassive black holes," says Barry McKernan, a research associate in the Department of Astrophysics at the American Museum of Natural History and an assistant professor at the Borough of Manhattan Community College (BMCC), City University of New York. "But no one put the two ideas together until now and said, 'Hey, maybe one is causing the other!'"

All galaxies are believed to host a supermassive black hole at their center, yet only a fraction of galactic centers show signs of brighter activity due to black hole feeding. The new research provides an explanation for the apparent conundrum: galactic centers which have sustained recent cloud impacts have enough fuel to light up by giving birth to hundreds of stars and feeding the central black hole. Galactic centers that have not been hit for a while (in cosmic terms, for more than about 10 million years) will be relatively inactive and their cores will appear normal.

"It's interesting that only some galaxies are active, even though we think every galaxy contains a supermassive black hole," says K. E. Saavik Ford, a research associate at the Museum and an assistant professor at BMCC. "The cloud bombardment idea provides an explanation: it's just random luck."

Fish oil may reduce risk of breast cancer

PHILADELPHIA — A recent report in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research, adds to the growing evidence that fish oil supplements may play a role in preventing chronic disease.

Researchers at the Fred Hutchinson Cancer Research Center in Seattle, Wash., led by Emily White, Ph.D., a member of the public health sciences division, asked 35,016 postmenopausal women who did not have a history of breast cancer to complete a 24-page questionnaire about their use of non-vitamin, non-mineral "specialty" supplements in the Vitamins and Lifestyle (VITAL) cohort study.

After six years of follow-up, 880 cases of breast cancer were identified using the Surveillance, Epidemiology and End Results registry.

Regular use of fish oil supplements, which contain high levels of the omega-3 fatty acids, EPA and DHA, was linked with a 32 percent reduced risk of breast cancer. The reduction in risk appeared to be restricted to invasive ductal breast cancer, the most common type of the disease.

The use of other specialty supplements, many of which are commonly taken by women to treat symptoms of menopause, was not associated with breast cancer risk.

This research is the first to demonstrate a link between the use of fish oil supplements and a reduction in breast cancer. Studies of dietary intake of fish or omega-3 fatty acids have not been consistent.

"It may be that the amount of omega-3 fatty acids in fish oil supplements are higher than most people would typically get from their diet," White said.

However, White cautioned against gleaning any recommendations from the results of one study.

"Without confirming studies specifically addressing this," she said, "we should not draw any conclusions about a causal relationship."

Edward Giovannucci, M.D., Sc.D., professor of nutrition and epidemiology at the Harvard School of Public Health and an editorial board member of Cancer Epidemiology, Biomarkers and Prevention, agreed.

"It is very rare that a single study should be used to make a broad recommendation," said Giovannucci. "Over a period of time, as the studies confirm each other, we can start to make recommendations."

Still, fish oil continues to excite many, as evidence emerges about its protective effect on cardiovascular disease and now cancer.

Harvard researchers are currently enrolling patients for the randomized Vitamin D and Omega-3 Trial (also called VITAL), which will assess the impact of fish oil supplements and vitamin D on cancer, heart disease and stroke.

The researchers plan to enroll 20,000 U.S. men aged 60 years and older and women aged 65 years and older who do not have a history of these diseases and have never taken supplements.

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