Posts tagged type II diabetes
Articles and news from the latest research reports.
Type II diabetes and the Alzheimer’s connection
A research team in Israel has devised a novel approach to identifying the molecular basis for designing a drug that might one day decrease the risk diabetes patients face of developing Alzheimer’s disease. The team will present its work at the 57th Annual Meeting of the Biophysical Society (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa.
A recent study suggests that people who suffer from type 2 diabetes face twice the risk of developing Alzheimer’s disease later in life compared to those who do not have diabetes. The link these diseases share relates to the formation of two types of peptide deposits that aggregate, or clump together. Peptides are chains of amino acids; longer chains form proteins. One type of peptide, called amyloid beta, is found in Alzheimer plaques in neurons of the brain. The other type, amylin, is found in the pancreas and the brain. Two years ago, researchers found both molecules in the pancreas of diabetic patients, and in both diseases their presence has been linked to the progression of the disease state.
To explore the hypothesis that interactions between the two molecules might play a critical role in the self-assembly of peptides that leads to protein aggregation, Yifat Miller, assistant professor from Ben-Gurion University of the Negev, Beer-Sheva, Israel, characterized the way the two protein molecules interact with each other through an examination of their structure. It was the first analysis of its kind.
"By identifying the specific ‘hot regions’ of these peptides that strongly interact with each other, our study may provide insight into the link between type 2 diabetes and Alzheimer’s disease," Miller says. "We believe that preventing these interactions by developing a drug will decrease the risk that type 2 diabetes patients face of developing Alzheimer’s disease later life."
(Source: eurekalert.org)
A landmark discovery about how insulin docks on cells could help in the development of improved types of insulin for treating both type 1 and type 2 diabetes.
For the first time, researchers have captured the intricate way in which insulin uses the insulin receptor to bind to the surface of cells. This binding is necessary for the cells to take up sugar from the blood as energy.
The research team was led by the Walter and Eliza Hall Institute and used the Australian Synchrotron in Melbourne. The study was published in the journal Nature.
For more than 20 years scientists have been trying to solve the mystery of how insulin binds to the insulin receptor. A research team led by Associate Professor Mike Lawrence, Dr Colin Ward and Dr John Menting have now found the answer.
Associate Professor Lawrence from the institute’s Structural Biology division said the team was excited to reveal for the first time a three-dimensional view of insulin bound to its receptor. “Understanding how insulin interacts with the insulin receptor is fundamental to the development of novel insulins for the treatment of diabetes,” Associate Professor Lawrence said. “Until now we have not been able to see how these molecules interact with cells. We can now exploit this knowledge to design new insulin medications with improved properties, which is very exciting.”
The Australian Synchrotron’s MX2 microcrystallography beamline was critical to the project’s success. “If we did not have this fantastic facility in Australia and their staff available to help us, we would simply not have been able to complete this project,” Associate Professor Lawrence said.
Associate Professor Lawrence assembled an international team of project collaborators, including researchers from Case Western Reserve University, the University of Chicago, the University of York and the Institute of Organic Chemistry and Biochemistry in Prague. “Collaborations in this field are essential,” he said. “No one laboratory has all the resources, expertise and experience to take on a project as difficult as this one.”
“We have now found that the insulin hormone engages its receptor in a very unusual way,” Associate Professor Lawrence said. “Both insulin and its receptor undergo rearrangement as they interact – a piece of insulin folds out and key pieces within the receptor move to engage the insulin hormone. You might call it a ‘molecular handshake’.”
Australia is facing an increasing epidemic of type 2 diabetes. There are now approximately one million Australians living with diabetes and around 100,000 new diagnoses each year.
“Insulin controls when and how glucose is used in the human body,” Associate Professor Lawrence said. “The insulin receptor is a large protein on the surface of cells to which the hormone insulin binds. The generation of new types of insulin have been limited by our inability to see how insulin docks into its receptor in the body.
“Insulin is a key treatment for diabetics, but there are many ways that its properties could potentially be improved,” Associate Professor Lawrence said. “This discovery could conceivably lead to new types of insulin that could be given in ways other than injection, or an insulin that has improved properties or longer activity so that it doesn’t need to be taken as often. It may also have ramifications for diabetes treatment in developing nations, by creating insulin that is more stable and less likely to degrade when not kept cold, an angle being pursued by our collaborators. Our findings are a new platform for developing these kinds of medications.”
Study uncovers protein key to fighting and preventing obesity
University of Florida researchers and colleagues have identified a protein that, when absent, helps the body burn fat and prevents insulin resistance and obesity. The findings from the National Institutes of Health-funded study were published online ahead of print Sunday, Jan. 6, in the journal Nature Medicine.
The discovery could aid development of drugs that not only prevent obesity, but also spur weight loss in people who are already overweight, said Dr. Stephen Hsu, one of the study’s corresponding authors and a principal investigator with the UF Sid Martin Biotechnology Development Institute.
One-third of adults and about 17 percent of children in the United States are obese, according to the Centers for Disease Control and Prevention. Although unrelated studies have shown that lifestyle changes such as choosing healthy food over junk food and increasing exercise can help reduce obesity, people are often unable to maintain these changes over time, Hsu said.
“The problem is when these studies end and the people go off the protocols, they almost always return to old habits and end up eating the same processed foods they did before and gain back the weight they lost during the study,” he said. Developing drugs that target the protein, called TRIP-Br2, and mimic its absence may allow for the prevention of obesity without relying solely on lifestyle modifications, Hsu said.
First identified by Hsu, TRIP-Br2 helps regulate how fat is stored in and released from cells. To understand its role, the researchers compared mice that lacked the gene responsible for production of the protein, with normal mice that had the gene.
They quickly discovered that mice missing the TRIP-Br2 gene did not gain weight no matter what they ate — even when placed on a high-fat diet — and were otherwise normal and healthy. On the other hand, the mice that still made TRIP-Br2 gained weight and developed associated problems such as insulin resistance, type 2 diabetes and high cholesterol when placed on a high-fat diet. The normal and fat-resistant mice ate the same amount of food, ruling out differences in food intake as a reason why the mice lacking TRIP-Br2 were leaner.
“We had to explain why the animals eating so much fat were remaining lean and not getting high cholesterol. Where was this fat going?” Hsu said. “It turns out this protein is a master regulator. It coordinates expression of a lot of genes and controls the release of the fuel form of fat and how it is metabolized.”
When functioning normally, TRIP-Br2 restricts the amount of fat that cells burn as energy. But when TRIP-Br2 is absent, a fat-burning fury seems to occur in fat cells. Although other proteins have been linked to the storage and release of fat in cells, TRIP-Br2 is unique in that it regulates how cells burn fat in a few different ways, Hsu said. When TRIP-Br2 is absent, fat cells dramatically increase the release of free fatty acids and also burn fat to produce the molecular fuel called ATP that powers mitochondria — the cell’s energy source. In addition, cells free from the influence of TRIP-Br2 start using free fatty acids to generate thermal energy, which protects the body from exposure to cold.
“TRIP-Br2 is important for the accumulation of fat,” said Dr. Rohit N. Kulkarni, also a senior author of the paper and an associate professor of medicine at Harvard Medical School and the Joslin Diabetes Center. “When an animal lacks TRIP-Br2, it can’t accumulate fat.”
Because the studies were done mostly in mice, additional studies are still needed to see if the findings translate to humans.
“We are very optimistic about the translational promise of our findings because we showed that only human subjects who had the kind of fat (visceral) that becomes insulin-resistant also had high protein levels of TRIP-Br2,” Hsu said.
“Imagine you are able to develop drugs that pharmacologically mimic the complete absence of TRIP-Br2,” Hsu said. “If a patient started off fat, he or she would burn the weight off. If people are at risk of obesity and its associated conditions, such as type 2 diabetes, it would help keep them lean regardless of how much fat they ate. That is the ideal anti-obesity drug, one that prevents obesity and helps people burn off excess weight.”
(Source: news.ufl.edu)
Pioneering Research on Type 2 Diabetes
While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to Type 2 diabetes, autoimmune diseases, and neurodegenerative diseases, among others.
Scientists at UCSB have published groundbreaking results of a study of Type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease.
The current work is based on a previous major finding by UCSB’s Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids. Marth is a professor in the Department of Molecular, Cellular, and Developmental Biology and the Biomolecular Science and Engineering Program; and holds the John Carbon Chair in Biochemistry and Molecular Biology and the Duncan and Suzanne Mellichamp Chair in Systems Biology. He is also a professor with the Sanford-Burnham Medical Research Institute in La Jolla.
"By studying the four types of components that make up the cell, we can, for the first time, begin to understand what causes many of the common grievous diseases that exist in the absence of definable genetic variation, but, instead, are due to environmental and metabolic alterations of our cells," said Marth. UCSB is the only institution studying these four types of molecules in the cells while also using computational modeling to determine their functions in health and disease, according to Marth.
The new study, published in the December 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of Type 2 diabetes.
The Case for Drinking as Much Coffee as You Like
"What I tell patients is, if you like coffee, go ahead and drink as much as you want and can," says Dr. Peter Martin, director of the Institute for Coffee Studies at Vanderbilt University. He’s even developed a metric for monitoring your dosage: If you are having trouble sleeping, cut back on your last cup of the day. From there, he says, "If you drink that much, it’s not going to do you any harm, and it might actually help you. A lot."
Officially, the American Medical Association recommends conservatively that “moderate tea or coffee drinking likely has no negative effect on health, as long as you live an otherwise healthy lifestyle.” That is a lackluster endorsement in light of so much recent glowing research. Not only have most of coffee’s purported ill effects been disproven — the most recent review fails to link it the development of hypertension — but we have so, so much information about its benefits. We believe they extend from preventing Alzheimer’s disease to protecting the liver. What we know goes beyond small-scale studies or limited observations. The past couple of years have seen findings, that, taken together, suggest that we should embrace coffee for reasons beyond the benefits of caffeine, and that we might go so far as to consider it a nutrient.
The most recent findings that support coffee as a panacea will make their premiere this December in the American Journal of Clinical Nutrition. Coffee, researchers found, appears to reduce the risk of type 2 diabetes.
Ultrasound Can Be Tweaked to Stimulate Different Sensations
A century after the world’s first ultrasonic detection device – invented in response to the sinking of the Titanic – Virginia Tech Carilion Research Institute scientists have provided the first neurophysiological evidence for something that researchers have long suspected: ultrasound applied to the periphery, such as the fingertips, can stimulate different sensory pathways leading to the brain.
And that’s just the tip of the iceberg. The discovery carries implications for diagnosing and treating neuropathy, which affects millions of people around the world.
“Ideally, neurologists should be able to tailor treatments to the specific sensations their patients are feeling,” said William “Jamie” Tyler, an assistant professor at the Virginia Tech Carilion Research Institute, who led the study published this week in PLOS ONE.
“Unfortunately, even with today’s technologies, it’s difficult to stimulate certain types of sensations without evoking others. Pulsed ultrasound allows us to selectively activate functional subsets of nerve fibers so we can study what happens when you stimulate, for example, only the peripheral fibers and central nervous system pathways that convey the sensation of fast, sharp pain or only those that convey the sensation of slow, dull, throbbing pain.”
Novel Antibodies for Combating Alzheimer’s and Parkinson’s Disease
Antibodies developed by researchers at Rensselaer Polytechnic Institute are unusually effective at preventing the formation of toxic protein particles linked to Alzheimer’s disease and Parkinson’s disease, as well as Type 2 diabetes, according to a new study.
The onset of these devastating diseases is associated with the inappropriate clumping of proteins into particles that are harmful to cells in the brain (Alzheimer’s disease and Parkinson’s disease) and pancreas (Type 2 diabetes). Antibodies, which are commonly used by the immune system to target foreign invaders such as bacteria and viruses, are promising weapons for preventing the formation of toxic protein particles. A limitation of conventional antibodies, however, is that high concentrations are required to completely inhibit the formation of toxic protein particles in Alzheimer’s, Parkinson’s, and other disorders.
To address this limitation, a team of researchers led by Rensselaer Professor Peter Tessier has developed a new process for creating antibodies that potently inhibit formation of toxic protein particles. Conventional antibodies typically bind to one or two target proteins per antibody. Antibodies created using Tessier’s method, however, bind to 10 proteins per antibody. The increased potency enables the novel antibodies to prevent the formation of toxic protein particles at unusually low concentrations. This is an important step toward creating new therapeutic molecules for preventing diseases such as Alzheimer’s and Parkinson’s.
“It is extremely difficult to get antibodies into the brain. Less than 5 percent of an injection of antibodies into a patient’s blood stream will enter the brain. Therefore, we need to make antibodies as potent as possible so the small fraction that does enter the brain will completely prevent formation of toxic protein particles linked to Alzheimer’s and Parkinson’s disease,” said Tessier, assistant professor in the Howard P. Isermann Department of Chemical and Biological Engineering at Rensselaer. “Our strategy for designing antibody inhibitors exploits the same molecular interactions that cause toxic particle formation, and the resulting antibodies are more potent inhibitors than antibodies generated by the immune system.”
Results of the new study, titled “Rational design of potent domain antibody inhibitors of amyloid fibril assembly,” were published online last week by the journal Proceedings of the National Academy of Sciences (PNAS).
New Treatment Aids Weight Loss, Improves Diabetes in Monkeys
A new, lab-created antibody that mimics the action of a naturally occurring molecule causes weight loss in monkeys, researchers report.
The engineered antibody also appears to improve insulin sensitivity, which could fight type 2 diabetes, and it decreases levels of triglycerides, a blood fat that contributes to hardening of the arteries.
"The results we describe in animal models are profound and very encouraging," said study senior author Yang Li, scientific director at Amgen, Inc., in Thousand Oaks, Calif. "While we’re excited about these findings, we’re still evaluating the results."
Li said it’s important to remember these findings were in monkeys and only in a preclinical setting. It’s not yet clear how this treatment might act in humans.
The study was funded by Amgen, the developer of the new treatment. The findings are published in the Nov. 28 issue of Science Translational Medicine.
(Image: Courtesy of iStockphoto/GlobalP)
Risk of childhood obesity can be predicted at birth
A simple formula can predict at birth a baby’s likelihood of becoming obese in childhood, according to a study published in the open access journal PLOS ONE.
The formula, which is available as an online calculator, estimates the child’s obesity risk based on its birth weight, the body mass index of the parents, the number of people in the household, the mother’s professional status and whether she smoked during pregnancy.
The researchers behind the study hope their prediction method will be used to identify infants at high risk and help families take steps to prevent their children from putting on too much weight.
New Diabetes Biomarkers Could Help Develop New Treatments
Researchers from the German Institute of Human Nutrition and the Max Delbrueck Center for Molecular Medicine recently revealed that they have been able to identify 14 new biomarkers for type 2 diabetes. The findings are important, as scientists believe that these biomarkers may be able to help in the development of new treatments to help prevent the disease. The scientists also believe that the results of the study will help them understand the various elements that contribute to the development of type 2 diabetes.