Nav: Home

Finding new clues to a sugar suspect in birth defects

June 22, 2016

BOSTON - (June 22, 2016) - Most pregnant women with well-controlled diabetes give birth to healthy children. But their babies run much higher risks of birth defects than babies born to women without diabetes, because very early in embryonic development, the babies are exposed to higher levels of glucose in maternal blood. In research done in mice, researchers at Joslin Diabetes Center have uncovered new clues about the role that glucosamine, another sugar that circulates in blood, can play in early embryonic development.

If glucosamine performs similarly in humans, understanding its role eventually may aid in avoiding birth defects, says Mary Loeken, Ph.D., an Investigator in the Section on Islet and Regenerative Cell Biology at Joslin Diabetes Center and an Associate Professor of Medicine at Harvard Medical School. Moreover, her work suggests an approach to developing stem cells that might help to strengthen future regenerative therapies for many diseases.

"The implications of this research go beyond the diabetic population," says Dr. Loeken, senior author of a paper published on June 17 in Scientific Reports.

Dr. Loeken, who studies how diabetes drives changes in the early embryo that lead to birth defects, began looking at a gene called GLUT2 after other researchers showed that it is activated in mouse embryos. GLUT2 can transport glucose from blood into cells, but it doesn't perform this efficiently unless the levels of glucose are very high. So what was its role in embryonic development?

Studying mouse models of diabetes, Dr. Loeken and her team first showed that modifying the mice genetically to lack GLUT2 protected the mice from producing embryos suffering from malformations when the mothers were diabetic. However, the Joslin scientists also found evidence suggesting that fewer of these embryos were surviving even when the mothers were not diabetic. This indicated that GLUT2 performs some function that is important for early embryonic survival.

Other researchers had shown that GLUT2 also can transport glucosamine, but whether GLUT2 functions as a glucosamine transporter under normal conditions has not been demonstrated. Dr. Loeken thought that embryo cells may need to obtain glucosamine from the mother's circulation. To examine the role of glucosamine, which can't be effectively adjusted in live animals, the Loeken lab created a line of mouse embryonic stem cells with activated GLUT2 that was grown in a culture with levels of glucose that are normal in mouse blood--unlike most stem cells, which are grown in very high levels of glucose.

In their latest paper, the investigators showed that GLUT2 can move glucosamine into these stem cells, and giving the cells this sugar greatly increased their rates of proliferation, while not having much effect on the ways they differentiated into other forms of more specialized cells.

Boosting proliferation could help embryos develop normally. Early embryos are "rapidly proliferating sets of cells," Dr. Loeken says. "They need to make more of themselves and they need to grow in size."

Among its functions in the cell, glucosamine is needed to assist in protein processing and the creation of signaling proteins. Cells can make glucosamine from glucose, but that takes away critical resources from energy production and building blocks for cell growth. "If a cell can't take up glucosamine, it will sort of starve," she says, so GLUT2 is critical. Additionally, she says, her research suggests that glucosamine, under some conditions, may be considered an essential nutrient for embryonic cells.

However, the GLUT2 protein also can play a destructive role if the maternal blood has high levels of glucose. "GLUT2 is not a very good glucose transporter under normal conditions, but when glucose levels are high it transports glucose very efficiently," Dr. Loeken points out. "So if the mother has diabetes, it could allow the embryo to act like a glucose sponge."

Her earlier research in mice embryos revealed that exposure to high blood glucose levels for a little as one day can produce a high rate of defects in the neural tube, the predecessor to the brain and spinal cord.

"Additionally, at high glucose concentrations, transport of glucosamine is significantly inhibited," Dr. Loeken adds. "This suggests that the adverse effects of high glucose on embryos are not just that more glucose is getting into cells, but also that less glucosamine is being taken up. Therefore, the beneficial effects of glucosamine on growth may be compromised."

Dr. Loeken cautions that no one has yet shown whether GLUT2 is expressed in human embryos, although research by other investigators has shown a correlation between mutations of GLUT2 in humans and risk of neural tube defects.

Her work also suggests that the high proliferation ability of mouse embryonic stem cells created in normal levels of glucose with activated GLUT2 may help to point the way for generating stem cells for future regenerative medicine treatments.

Most researchers now engineering embryonic stem cells or embryonic-like "induced pluripotent stem cells", with either mouse or human cells, grow them in glucose levels that are much higher than is normal in the body. That means that the metabolism of these new cells doesn't match the conditions the cells may find at the organ they are meant to repair

Today, glucosamine tablets are sold for joint pain, but they are not recommended for pregnant women, a point that Dr. Loeken stresses. Glucosamine mechanisms in humans are not fully understood, and there are unfavorable effects when glucosamine levels get too high. Even if adding small amounts of glucosamine eventually might be proven to be helpful, achieving the right levels in a pregnant woman's blood "would be a delicate balance," she says.
Joslin's Jin Hyuk Jung was first author on the paper. Kumiko Iwabuchi and Zhihong Yang were co-authors. The work was funded by the National Institutes of Health.

About Joslin Diabetes Center

Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is an independent, non-profit institution affiliated with Harvard Medical School, and one of only 11 NIH-designated Diabetes Research Centers in the U.S.

Joslin Diabetes Center

Related Diabetes Articles:

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.
Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.
Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at