Half Of Americans Have Gene That Affects How Body Burns Sugar

A recent study by a Saint Louis University researcher confirms findings that about half of the U.S. population has a version of a gene that causes them to metabolize food differently, putting them at greater risk of developing diabetes.

Edward Weiss, Ph.D., assistant professor of nutrition and dietetics at Doisy College of Health Sciences at Saint Louis University, looked at a relatively common version of a gene called FABP2, which is involved in the absorption of fat from food.

Those people with the variant gene processed fat differently than those who don’t have it. They burned more fat, which may have hindered their ability to remove sugar from the blood stream and burn it. Diabetes is characterized by too much sugar in the blood.

“This study adds to what was previously known about this gene variant by showing that after consuming a very rich milkshake, people with the variant gene process the fat from the drink differently than other people,” Weiss says.

That is not to say that half of U.S. residents are destined to get diabetes, he adds.

“While the variation of the gene appears to contribute to the diabetes risk, it does not cause diabetes by itself,” Weiss says.

“Many other genes, some known and some unknown, are involved in a person’s overall risk of developing diabetes. Those are things a person can’t control. But there are risk factors for diabetes that a person can change — lifestyle factors, such as diet and exercise.”

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The study was published in the January issue of the American Journal of Clinical Nutrition.

Contact: Nancy Solomon
Saint Louis University

Allergic Rhinitis Associated With Decline In Work And School Performance

Allergic rhinitis (AR), more commonly known as “hay fever” can have a profound impact on the daily lives of sufferers beyond its physical effect — including psychological well-being, sleep quality, and ability to learn and process cognitive input, according to a new article scheduled to appear in the on-line issue of Allergy and Asthma Proceedings.

“The Burden of Allergic Rhinitis,” authored by Robert A. Nathan, M.D., Clinical Professor of Medicine, Department of Internal Medicine, Division of Allergy and Immunology, University of Colorado Health Sciences Center, provides an overview of the impact of AR in our society based on findings in the landmark 2006 Allergies in America Survey (AIA) and other noteworthy surveys and studies conducted in the US and Europe. In his article, Dr. Nathan describes the negative cascade of events that adults and children can experience as a result of this condition.

“Nasal congestion profoundly affects quality of life, largely by undermining the restorative power of sleep. Poor-quality sleep leads to daytime drowsiness, fatigue, indecision and significant impairment in learning and cognition,” he writes. “As a result, adults become moody, less efficient, and more likely to experience work-related injury; children are prone to be shy and may also become depressed, anxious or fearful.”

Consequently, presenteeism (decreased productivity at work due to illness) and school absenteeism (habitual absence) escalate.

Lack of Effectiveness of Currently Available Intranasal Sprays

While intranasal corticosteroids are the gold standard for symptom control, patients report problems with effectiveness of currently available options. Only 16 percent of respondents in the AIA survey indicated that intranasal corticosteroids provide relief for all their symptoms, and almost half (48 percent) said they fail to provide 24-hour symptom relief.

“Patients self-adjust their use of over-the-counter and prescription products, but find that currently available options do not always provide the 24-hour relief, and if they do, there are bothersome side effects,” explains Dr. Nathan. Consequently, the author concludes that there is a need for new nasal allergy medications that provide complete 24-hour symptom relief that is sustained over time.

About Allergies in America Survey

The Allergies in America survey is a landmark survey sponsored by ALTANA Pharma US, Inc. and is the largest survey ever conducted in a population of allergic rhinitis sufferers and healthcare practitioners. Analysis of the data from the 2,500 allergy sufferers and 400 physicians, nurse practitioners and physician assistants provides a window into to the behavioral and psychosocial effects of AR.

Asthma & Allergy Associates
http://www.texallergy.com/locations.htm

FDA Approves NovoLog(R) Category Change For Use In Pregnant Women With Type 1 Diabetes

Novo Nordisk announced today that the United States Food and Drug Administration (FDA) has approved NovoLog(R) (insulin aspart [rDNA origin] injection) for pregnancy Category B rating, further validating NovoLog(R) as a safe and effective treatment for pregnant women with Type 1 diabetes and their unborn children.

Diabetes and its treatment options can present significant challenges for women wishing to conceive and have a healthy pregnancy. As a safety precaution, the FDA classifies prescription drugs with specific category ratings to provide decision-making guidelines for physicians treating pregnant women. The Pregnancy Category B rating for NovoLog(R) indicates that adequate studies in pregnant women with Type 1 diabetes have demonstrated that NovoLog(R) does not increase risk to the unborn baby. Previously, NovoLog(R) was classified as a Category C rating, which indicates that adverse effects on the fetus have been demonstrated in animal reproduction studies, and that adequate and well-controlled studies in pregnant women have not been conducted to demonstrate safety(1).

“While clinical research is rarely conducted in pregnant women, we at Novo Nordisk understand the needs of this special population. The confirmed safety of NovoLog(R) will allow their doctors to make informed decisions about treatment options for people with diabetes,” said Martin Soeters, president of Novo Nordisk. “We are excited that the FDA has acknowledged our efforts to advance diabetes treatment and recognizes the value of our insulin analogs such as NovoLog(R).”

The FDA category change was based on a review of the largest ever randomized controlled trial using an insulin analog in pregnant women with type 1 diabetes.

The study, conducted at 63 sites in 18 countries, compared the safety and efficacy of NovoLog(R) versus human regular insulin (HRI) in the treatment of 322 pregnant women with type 1 diabetes. Data demonstrated that changes in HbA1c and rates of maternal hypoglycemia were comparable with NovoLog(R) compared to HRI. The study was not large enough to evaluate the risk of congenital malformations. Compared to HRI, the trial with NovoLog(R) showed improved outcomes for both mother and child in terms of:

— Fewer preterm deliveries (p
— Reduced risk of neonatal hypoglycemia (glucose
— Consistently low rates of major hypoglycemia

— Reduced risks to the fetus, with outcomes at least comparable to HRI(2).

Diabetes and Pregnancy

Each year in the US, about 18,000 women with pre-existing type 1 or type 2 diabetes(3) become pregnant and 135,000 pregnant women develop gestational diabetes (those who develop high blood sugar during pregnancy(4). For these pregnant women, insulin is frequently used to manage their diabetes(5).

Diabetes that is not tightly controlled can lead to extensive complications for mother and baby and can cause significant burdens on families and the healthcare system(6):

— For the mother, complications from existing diabetes may worsen and new complications may emerge(7), including greater incidence of miscarriage, high blood pressure, kidney disease and nerve damage(8).

— For the baby, uncontrolled diabetes may mean up to four-times more likelihood of being born with increased infant mortality, preterm birth (and the myriad of problems associated with it), high birth weight(9) or a birth defect(10).

Chances of these complications are lower when women have good glycemic control(11). However, only 40-60 percent of women with pre-existing diabetes achieve optimal glycemic control while pregnant(12).

About NovoLog(R)

NovoLog(R) is a rapid-acting form of insulin for the treatment of people with diabetes mellitus for the control of hyperglycemia. It enters the bloodstream quickly and begins working within minutes to lower blood glucose. The rapid onset and short duration of action mimic the insulin action of a person without diabetes. NovoLog(R) offers convenient mealtime dosing and should be administered before a meal (start of meal within 5 to 10 minutes after injection). NovoLog is available in the prefilled NovoLog(R) FlexPen(R) insulin delivery system.

NovoLog(R) is contraindicated during episodes of hypoglycemia and in people hypersensitive to insulin aspart or one of its excipients. Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog(R). See package insert for more details. NovoLog(R) was originally approved by the FDA for use in adults in the U.S. in 2000.

Because it has a more rapid onset and shorter duration of action than regular human insulin, NovoLog(R) should normally be used in regimens together with an intermediate or long-acting insulin, and injection of NovoLog(R) should immediately be followed by a meal.

Any change in insulin should be made cautiously and only under medical supervision.

Prescribing information for NovoLog is available by contacting Novo Nordisk or by visiting http://www.novonordisk-us.com.

Novo Nordisk is a healthcare company with an 80-year history of innovation and achievement in diabetes care. In addition to diabetes care, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone therapy for women. Novo Nordisk’s business is driven by the Triple Bottom Line: a commitment to economic success, environmental soundness, and social responsibility to employees and customers. With headquarters in Denmark, Novo Nordisk employs more than 23,000 employees in 79 countries, and markets its products in 179 countries. Novo Nordisk’s B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol ‘NVO’. For global information, visit http://www.novonordisk.com; for United States information, visit http://www.novonordisk-us.com.

References

(1) “Current Categories for Drug Use in Pregnancy,” FDA (2006). http://www.fda.gov/fdac/features/2001/301_preg.html#categories

(2) Data on file at Novo Nordisk Inc.

(3) Centers for Disease Control and Prevention. Preventing Diabetes and Its Complications. Available at http://www.cdc.gov/nccdphp/publications/factsheets/Prevention/diabetes.htm. Accessed November 8, 2006.

(4) American Diabetes Association. Gestational Diabetes. Available at http://www.diabetes.org/gestational-diabetes.jsp. Accessed November 8, 2006.

(5) “Diabetes in Pregnancy,” March of Dimes (2006). http://www.marchofdimes.com/professionals/681_1197.asp

(6) Lanham, MD: “The Diabetes in Pregnancy Dilemma: Leading Change with Proven Solutions, University Press,” Journal of the American Medical Association book review (9/27/2006).

(7) “Pregnancy and Diabetes Frequently Asked Questions,” Centers for Disease Control (2006).

(8) “Diabetes and Pregnancy Frequently Asked Questions,” (2006), Centers for Disease Control. http://www.cdc.gov/ncbddd/bd/diabetespregnancyfaqs.htm

(9) Ibid.

(10) “High Blood Glucose Levels in Early Pregnancy May Deprive Embryo of Oxygen and Lead to Birth Defects, Joslin Diabetes Center Study Shows,” (2005) Joslin Diabetes Center

(11) “Diabetes and Pregnancy,” Organization of Teratology Services (2006). http://otispregnancy.org/pdf/diabetes.pdf

(12) Lanham, MD: “The Diabetes in Pregnancy Dilemma: Leading Change with Proven Solutions, University Press,” Journal of the American Medical Association book review (9/27/2006).

Novo Nordisk
http://www.novonordisk.com/

Global Survey Of The Consequences Of Small And Large DNA Variants In Our Genome

Findings published in Science will accelerate the search for genes involved in human disease. The report provides a first genome-wide view of how the unique composition of genetic variation within each of us leads to unique patterns of gene activity.

By defining those genetic variants with a biological effect, the results will help prioritise regions of the genome that are investigated for association with disease. This is an important step to understanding links between genes and disease for individuals, and across populations.

The Human Genome Project gave us the instruction manual for building a human. The HapMap and Copy Number Variation (CNV) Projects developed indices of where to find differences in the manuals of different people. One of the challenges for research into variation and disease is that most variants have no consequence for our wellbeing.

The new study gives a global view of the consequences of those differences for gene activity. The work shows that activity of more than 1000 genes is affected by sequence variation and is the first map of human populations that identifies the most important fraction of DNA variation, that which directly affects gene activity.

The research was led by scientists from the Wellcome Trust Sanger Institute, together with colleagues from the University of Cambridge, Hospital for Sick Children/University of Toronto and Harvard Medical School/Brigham and Women’s Hospital.

Using the HapMap series of cell samples from four populations, they measured the activity of more than 14,000 genes in cells grown in culture. The cell samples provide a snapshot of genetic activity in one cell type. The activity of each gene was then correlated with genetic variation nearby, as defined by the HapMap, an index of single-base changes (single nucleotide polymorphisms, or SNPs) and the new index of copy number variants (CNVs).

“We’ve been able to look back into our history and find changes that are older and likely to be shared among populations,” explained Dr Manolis Dermitzakis, senior author and Project Leader at the Wellcome Trust Sanger Institute. “But we also find many that are newer and less widespread.

“These are part of our recent evolution and a step along the way to understanding the origin and personal consequences of genetic change, not least for our wellbeing. This is a first generation map of biologically important DNA sequence variation”

The understanding of the genetic basis of gene activity will help medical research to provide individuals with information about their personal predisposition to disease.

The study was a massive undertaking: it included HapMap genotype data on 700,000 SNPs located close to genes, as well as 25,000 sites interrogated for potential structural variation to examine copy-number differences, looking at the activity of 14,000 genes in 210 unrelated individuals.

SNP and CNV variation correlated with altered activity in almost 900 and 240 genes, respectively. The HapMap has been invaluable in detecting variants involved in many diseases and these results suggest that the CNV index will prove similarly useful.

“The remarkable finding was that there is such little overlap in the genes found by using the two indices,” commented Dr Matthew Hurles, also a leader of the project at the Wellcome Trust Sanger Institute. “Only about 10% of the activity variants associated with a CNV were also associated with a SNP.

“This suggests that we must include CNV studies in our searches for genetic variation associated with disease or we will be missing a lot of the important genetic effects.”

The results show that at least 10-20% of heritable variation in gene activity is due to CNVs. The team found associations that included previously known examples, such as UGT2B17, which has been associated with prostate cancer, proving that the new approach works well.

They also showed for the first time that activity of other genes, located close to UGT2B17, was affected. Finding other effects in this way will enhance the search for critical genes within a region of genetic possibilities.

Some associations were not found in all four populations, two-thirds (CNVs or SNPs) being found in only one population. A gene implicated in Spinal Muscular Atrophy showed an association in three populations, but not in Yoruba from Ibadan, Nigeria. Understanding population differences can help us understand our history.

Variation in copy number can affect gene activity by altering the ‘dose’ of a gene, by disrupting the active parts of a gene that contain the code for protein, or by disrupting the regulatory regions of the genome that control gene activity – the on/off and dimmer switches in our genome.

“Although the simplest model for a CNV affecting gene activity is where the variant is a deletion of a gene or part of a gene, we found examples where activity is affected from a distance,” commented Barbara Stranger, first author and post-doctoral fellow at the Wellcome Trust Sanger Institute. “This may occur when the CNV reduces the effectiveness of a region that works to switch the genes on or off.”

The survey gives the first global view of the effects of SNPs and CNVs on gene activity. The methods and resources developed will help researchers better understand the link between differences – large and small – in our genome and our health.

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Publication details: Stranger BE et al. (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science

Matthew Hurles and Manolis Dermitzakis are corresponding authors.

Funding

Funding was provided by the Wellcome Trust, the National Institutes of Health, Cancer Research UK, the Leukemia and Lymphoma Society and the Brigham and Women’s Hospital Department of Pathology, the UK Medical Research Council, the Royal Society and Genome Canada/Ontario Genomics Institute.

Participating Centres

* Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

* Department of Oncology, University of Cambridge, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK

* Istituto di Tecnologie Biomediche-Sezione di Bari, Consiglio Nazionale della Ricerche (CNR), Bari, Italy

* Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

* Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA

* The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, MaRS Centre, Toronto, Ontario, Canada

* Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada

* Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA, USA.

Selected websites

GENEVAR – GENe Expression VARiation database

Copy Number Variation Project

Dr Dermitzakis’ research

Dr Hurles’ research

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992 as the focus for UK sequencing efforts. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms such as mouse and zebrafish, and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to enable the Institute to build on its world-class scientific achievements and exploit the wealth of genome data now available to answer important questions about health and disease. These programmes are built around a Faculty of more than 30 senior researchers. The Wellcome Trust Sanger Institute is based in Hinxton, Cambridge, UK. http://www.sanger.ac.uk/

The Wellcome Trust is the largest independent charity in the UK and the second largest medical research charity in the world. It funds innovative biomedical research, in the UK and internationally, spending around ВЈ500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

Contact: Don Powell
Wellcome Trust Sanger Institute

Model Homes Offer National IAQ Impact Results

Airborne contaminants in homes can range from allergic agents such as mold to potentially lethal threats such as carbon monoxide. Engineers at the National Institute of Standards and Technology (NIST) have developed a database of U.S. residential housing* to help conduct nationwide analyses of ventilation, air cleaning or moisture control strategies to reduce indoor air pollution.

Most people presume that the indoor air quality (IAQ) measures that rid one house of airborne contaminants should work in a similar house, but when it comes to ranking, on a regional or national scale, potentially expensive residential code or construction changes, housing and health authorities as well as homebuilders want more than conventional wisdom and supposition. They want data, and a lot of it. The new NIST set of more than 200 residential dwellings, representing 80 percent of the United States housing stock, can be combined with a computer simulation technique to determine the impacts of IAQ interventions.

NIST developed its database of model homes from the U.S. Census Bureau’s American Housing Survey (AHS) and the U.S. Department of Energy’s (DOE) Residential Energy Consumption Survey (RSECS). They then selected 209 dwellings as representative of 80 percent of U.S. housing stock. The homes, grouped into four categories–detached, attached, manufactured homes and apartments, were defined by their age, floor area, number of floors, foundation type and existence of a garage.

The engineers then developed floor plans for each house and created a model of each in NIST’s multizone indoor air quality and ventilation assessment computer program, CONTAM. Analysts can use the models to simulate and examine energy, IAQ and human exposure issues in a particular type of dwelling or all the dwellings as a group. Conclusions drawn from simulations with a particular house type should be valid for similar houses on a nationwide or regional level. The current multizone representations of the 209 dwellings created with CONTAM are available at http://www.bfrl.nist.gov/IAQanalysis along with floorplans of the buildings. The U.S. Department of Housing and Urban Development sponsored this work.

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*A. Persily, A. Musser and D. Leber. A collection of homes to represent the U.S. housing stock. NISTIR 7330, August 2006.

Contact: John Blair
National Institute of Standards and Technology (NIST)

Imaging Technique Is Highly Accurate In Diagnosing, Locating Pancreas Defects In Newborns

The noninvasive imaging technology called positron-emission tomography (PET scan) is extremely accurate in diagnosing a type of congenital hyperinsulinism (HI), a rare but severe imbalance of insulin levels in newborns. When that disease is confined to a limited section of the baby’s pancreas, the PET scan is 100 percent accurate in locating the abnormal spot, and guiding surgeons to curative, organ-sparing surgery.

A research team from The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine reported highly encouraging preliminary results from a study of 24 infants referred to the Hyperinsulinism Center at Children’s Hospital between December 2004 and November 2005. All the children had congenital hyperinsulinism that could not be controlled with medicine. If this condition goes uncontrolled, abnormally high insulin levels may cause irreversible brain damage. The study appeared in the February issue of the Journal of Pediatrics.

Congenital HI is caused by mutations that damage the insulin-secreting beta cells in the pancreas, which in an infant is smaller than an adult’s little finger. When the abnormal cells are limited to a discrete portion of the pancreas, the disease is focal; when the abnormal cells are distributed throughout the organ, the disease is diffuse. Accurate diagnosis is important because focal disease can be cured by surgically removing the focal lesions. In diffuse disease, surgeons may remove nearly the total pancreas, but that leaves the child at risk for later diabetes.

Using a mildly radioactive compound called 18F-fluoro-L-dihydroxyphenylalanine, or [18F]-DOPA, the researchers diagnosed focal or diffuse hyperinsulinism correctly in 23 of the 24 cases, for an accuracy of 96 percent. In the 11 cases with focal hyperinsulinism, the technique was 100 percent accurate in pinpointing the abnormal lesions. [18F]-DOPA binds to the lesions, which then are visible to the naked eye on a body scanner.

“When we compared our findings from the PET scan with pathological results, we found 100 percent agreement in locating the focal lesions,” said Olga T. Hardy, M.D., a pediatric endocrinologist at Children’s Hospital who was the study’s lead author. “This accuracy is superior to that of invasive, technically difficult techniques that measure insulin sampled from specific veins in an infant.”

The Congenital Hyperinsulinism Center at The Children’s Hospital of Philadelphia is the only facility of its kind in the country, and one of the few centers worldwide, with the knowledge and capability to successfully cure patients. Our specialists are true pioneers in the diagnosis and treatment of HI, offering patients the most innovative and compassionate care. The Center provides a multidisciplinary approach to care. Our sophisticated team of pediatric endocrinologists, surgeons, pathologists, anesthesiologists, nurses and researchers work closely together to provide seamless care on a full spectrum of services.

Charles A. Stanley, M.D., a pediatric endocrinologist at Children’s Hospital and co-author of this study is world-renowned for his research and for discovering several genetic mutations in HI.

Dr. Hardy added that a later study will report on findings in all 50 patients. If the preliminary results hold up, they may suggest that [18F]-DOPA PET imaging should become a standard of care in infants with congenital HI who require surgery.

Dr. Hardy’s co-authors were Miguel Hernandez-Pampaloni, M.D., Janet R. Saffer, M.D., Mariko Suchi, M.D., Eduardo Ruchell, M.D., Hongming Zhuang, M.D., Arupa Ganguly, M.D., N. Scott Adzick, M.D., Abass Alavi, M.D., and Charles A. Stanley, M.D., all of The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine.

About The Children’s Hospital of Philadelphia:

The Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

The Children’s Hospital of Philadelphia
http://www.chop.edu

Arkansas Bill Would Require Inmates To Receive HIV Test Before Being Paroled

Arkansas Rep. Fred Allen (R) on Thursday introduced a bill (HB 1444) in the state House that would require inmates in the state’s prisons to undergo tests for HIV and other sexually transmitted infections before being paroled, the AP/Today’s THV reports. The bill also would require that inmates receive treatment if they test positive for HIV or other STIs. According to Dina Tyler, spokesperson for the Arkansas Department of Correction, about 100 of the state’s 14,000 inmates are HIV-positive, and 25 to 30 have progressed to AIDS. The state requires that inmates be tested for hepatitis when entering the prison system, but HIV tests are voluntary. Tyler said prison officials are examining the bill to determine what the additional testing would cost (AP/Today’s THV, 2/8).

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

GMOs And Allergies: Tests May Help Answer Questions

The potential of genetically engineered foods to cause allergic reactions in humans is a big reason for opposition to such crops. Although protocols are in place to ask questions about the allergy-causing possibilities, there has been no test that offers definitive answers.

But all of that could change as a Michigan State University researcher has developed the first animal model to test whether genetically engineered foods could cause human allergic reactions. Venu Gangur, MSU assistant professor of food science and human nutrition, has received a $447,000 grant from the Environmental Protection Agency to validate the test.

Genetically engineered crops are created by inserting a protein from a different organism into the original crop’s genome. This is usually done to create a plant that is more resistant to insects or diseases.

The Food and Agriculture Organization within the World Health Organization has a structured approach to determining whether genetically engineered foods cause allergies, according to Gangur, who also is a faculty member in the National Food Safety and Toxicology Center. “But it has a major flaw. A critical question in that process asks, ‘Does the protein cause an allergic reaction in animals?’ The problem is that there has been no good animal model available to test this.”

Gangur and students in his lab have developed a mouse model – the first of its kind – to test the allergy-causing potential of genetically engineered foods. He’ll use the EPA grant to examine whether the model works on a variety of proteins. If successfully validated, the testing could be available commercially in about five years.

Perhaps the best known case of a genetically engineered crop potentially causing allergies was StarLink corn. Created by Aventis in 1996, StarLink contained the cry9C protein from a common soil bacterium, a strain of Bacillus thuringiensis. The cry9C protein protected the corn from several types of corn borers and black cutworms. StarLink was approved by the EPA for use in animal feed and nonfood products in 1998. But in 2000, fragments of cry9C DNA were detected in taco shells and other food products.

“Many people believed that StarLink was responsible for their asthma attacks and other allergic reactions,” Gangur said. “The Centers for Disease Control took samples and tried to figure out if StarLink was the cause, but the data were inconclusive. There was really no good method to determine if StarLink caused allergic reactions. This is why our model will be such a valuable tool. We’ll be able to determine the allergenic potential of genetically engineered crops before they’re released into the human or animal food chain.”

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Robert Tempelman, MSU professor of animal science and statistics and probability, is the project’s co-investigator.

Gale Strasburg, chairperson of the MSU Department of Food Science and Human Nutrition; and Jim Pestka and Maurice Bennink, MSU professors of food science and human nutrition, also are participating in the project.

The research of Gangur, Tempelman, Pestka and Bennink is supported by the Michigan Agricultural Experiment Station.

url: http://newsroom.msu.edu/site/indexer/2864/content.htm

Contact: Sue Nichols
American Society for Biochemistry and Molecular Biology

Major Link In Brain-Obesity Puzzle Found

Single protein in brain cells plays a key role in controlling body weight, response to insulin and leptin, and energy balance

A single protein in brain cells may act as a linchpin in the body’s weight-regulating system, playing a key role in the flurry of signals that govern fat storage, sugar use, energy balance and weight, University of Michigan Medical School researchers report.

And although it’s far too early to say how this protein could be useful in new strategies to fight the world’s epidemic of obesity, the finding gives scientists an important system to target in future research and the development of anti-obesity medications.

In the February issue of the Journal of Clinical Investigation, U-M researcher Liangyou Rui, Ph.D. and his team report their findings on a protein called SH2B1, and specifically on its activity in brain cells.

Using a variety of genetic, diet and hormone techniques, they were able to show that the action of SH2B1 regulates body weight, the action of the metabolic signaling molecules leptin and insulin, and the use of energy from food. It even moderated the impact of a high-fat diet on body weight.

The experiments were performed in mice, including two types of mice that the team altered genetically so that they only expressed a unique form of the SH2B1 protein in their brain cells. The protein occurs elsewhere in the body, but the researchers were able to zero in on its activity in the hypothalamus: the area of the brain that coordinates signals from the brain and body relating to food, hunger, and the balance of energy and nutrients in the body.

Previously, Rui and his team have shown that mice that lack the gene for SH2B1 — called knockout mice — become obese, diabetic, and unable to stop eating. Their bodies lose the ability to sense the signals sent by leptin and insulin that tell the brain to slow down food intake and fat storage.

For the new paper, they looked at not only normal mice and mice that didn’t have the SH2B1 gene, but also at mice that made SH2B1 only in brain cells, either in normal or larger-than-normal amounts. They found that restoring SH2B1 just in the brain completely corrected the metabolic disorders that the knockout mice had developed, but also improved the brain cells’ ability to respond to leptin signals and produce further signals that regulate eating.

What’s more, the mice that were treated to make extra SH2B1 didn’t become obese or lose their ability to respond to leptin signals even after being fed a high-fat diet that caused those effects in other mice.

“Obesity, whether in mice or humans, is the product of an altered balance between energy intake and energy use. The imbalance is linked to alterations in leptin and insulin signaling that lead to excess weight gain and Type 2 diabetes, respectively,” says Rui, an assistant professor of molecular and integrative physiology at U-M. “SH2B1 appears to play a key regulatory role in this system, through its direct influence on the processing of leptin and insulin signals in cells of the brain’s hypothalamus.”

Rui, who first discovered SH2B1’s metabolic importance as a graduate student at U-M in the 1990s, worked on the new paper with postdoctoral fellow Decheng Ren, Ph.D., who also collaborated on a paper in the journal Cell Metabolism in 2005 that first indicated SH2B1’s key role in obesity.

The team and other researchers have found that SH2B1, which was previously called SH2-B, is a kind of jack-of-all-trades in the world of cell signaling. Able to shuttle between the area just beneath the cell membrane and the nucleus, it can bind to many different molecules and facilitate signaling.

Specifically, it can bind to a variety of molecules called tyrosine kinases, including ones that serve as receptors for insulin and growth factors that circulate in the brain and body. One of its most important binding partners is JAK2, which is activated every time a leptin molecule binds to a cell.

Since leptin is the body’s messenger boy to the brain for “stop eating, we’re full” messages, and JAK2 helps receive those messages as they arrive, SH2B1’s partnership with JAK2 is an important one. In a previous paper, Rui and his former mentor and current colleague Christin Carter-Su, Ph.D., showed that SH2B1 encourages the action and production of JAK2, unlike two other proteins that have been shown by other teams to reduce its activity. Carter-Su is a professor of molecular and integrative physiology and heads the biomedical research division of the Michigan Diabetes Research and Training Center.

In addition to revealing the importance of SH2B1 activity in the brain, the new paper shows that SH2B1 is expressed in four different forms in many tissues of the body, including fat cells known as adipose tissue, as well as the liver, heart, pancreas and muscle.

Rui and his team also explored the role of SH2B1 in fat cells, finding that the knockout mice that lacked the SH2B1 gene stored away much more fat than normal mice, and had much larger fat cells – giving them two-and-a-half times more body fat content than normal mice. The mice that had some of their SH2B1 restored in just their brains by genetic alteration did not experience this – and in fact had less fat than normal mice.

Since these mice lacked the ability to make SH2B1 in their fat cells, the authors suspect that fat-cell SH2B1 encourages the storing of fat. When they tested this theory, they found that SH2B1 appeared to help mouse embryonic cells turn into fat cells, a process called adipogenesis. But, they suspect, the action of SH2B1 in the brain trumps its action in fat tissue, leading to the development of obesity in mice that lack SH2B1 in both locations.

Rui and his team now hope to explore SH2B1’s role in the brain and body even further, and hope to translate their findings into clinical research involving humans. They hope that their findings will help lead to better tactics for understanding the causes of obesity and its consequences, including Type 2 diabetes, and perhaps better methods for preventing and reversing them.

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U-M has filed for patent protection on the earlier paper referenced in this work, and is seeking a licensing partner to bring these drug-discovery methods to market. In addition to Rui and Ren, the paper’s authors are postdoctoral fellows Yingjiang Zhou, Ph.D., Minghua Li, Ph.D. and Zhiqin Li, Ph.D. and graduate student David Morris. The research was supported by the National Institutes of Health and the American Diabetes Association. Reference: Journal of Clinical Investigation, DOI 10.1172/JCI29417

Contact: Kara Gavin
University of Michigan Health System

Groups Call On G8 To Deliver On 2005 Promises Made For African Development, Including Universal Access To HIV/AIDS Treatment

Some HIV/AIDS advocacy groups last week called on finance ministers from the Group of Seven industrialized nations, meeting on Friday in Germany, to fulfill commitments made by the Group of Eight industrialized nations at its 2005 summit regarding aid to Africa, including HIV/AIDS funding, South Africa’s Star reports (Pienaar, Star, 2/9). G8 leaders in July 2005 at the close of their summit in Gleneagles, Scotland, agreed to an immediate doubling of aid to Africa to $50 billion annually in order to fight poverty and disease on the continent. The final summit communique officially endorsed a debt relief plan, which canceled at least $40 billion in debt owed by the world’s 18 poorest nations. The communique also included an agreement on providing universal access to HIV/AIDS treatment, according to British Prime Minister Tony Blair (Kaiser Daily HIV/AIDS Report, 1/29). According to a report from ActionAid International, Germany, Italy, Japan and the U.S. have made no attempts to meet the target of universal access to antiretrovirals by 2010, London’s Guardian reports. G8 countries still need to establish a funding plan to meet the treatment access goal, the report says, adding that although 1.6 million HIV-positive people worldwide have access to antiretrovirals, 5.2 million still need access (Elliott, Guardian, 2/8). Oxfam in a statement released Thursday called on G8 nations to deliver on promises made in Gleneagles, adding that significant funding increases are needed to meet the U.N. Millennium Development Goals by 2015. According to Oxfam, development aid decreased by 2.1% in 2005. “The G8 has a choice,” Max Lawson of Oxfam said, adding, “Will 2007 be yet another year of broken promises to Africa or the year they finally put their words into action?” He added, “Germany has got to take the lead on this” (Star, 2/9). According to Aditi Sharma, international HIV/AIDS coordinator of ActionAid India, G8 nations should allocate $8 billion in 2007 and $10 billion annually thereafter to achieve the goal of universal access to treatment by 2010 (De Capua, VOA News, 2/8). Germany, which this year heads the G8, has agreed to put Africa on the agenda for this year’s summit in Heiligendamm, Germany (Guardian, 2/8).

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.