Obesity and Diabetes – Is Your Gut in Control?

August 28, 2015 by

Aug. 21, 2015

By Medical Discovery News

Your body is like a forest, providing a home to microscopic flora and fauna. In fact, your body is home to up to 100 times more microbes than your own cells, which make up your microbiome. While we provide them residence, these microbes help us out by providing a first line of defense against disease trying to invade our bodies, even breaking down food during digestion and producing vitamins. Now, the microbes that live in the digestive tract are helping us understand diabetes better.

According to the Human Microbiome Project sponsored by the National Institutes of Health, the microbiome plays a huge role in human health. When the microbiome is altered or imbalanced, it can cause conditions like obesity, irritable bowel syndrome, skin disease, urogenital infection, allergy, and can even affect emotion and behavior.

Recently, scientists from Israel discovered another surprising effect of the microbiome while investigating the use of artificial sweeteners in relation to glucose intolerance and diabetes. Artificial sweeteners such as saccharin, sucralose, and aspartame are commonly used in weight loss strategies because they do not add calories while still satisfying sweet cravings. However, artificial sweeteners are not always effective in managing weight and glucose, and scientists at the Weizmann Institute of Science may have figured out why.

Through experimentation they observed that adding artificial sweeteners to the diets of mice caused significant metabolic changes, including increasing blood sugar levels more than mice fed regular sugar. It didn’t matter whether the mouse was obese or at a normal weight, they all reacted the same. Dietary changes can alter the populations of bacteria in our guts, so the study addressed whether those changes affected blood glucose levels as well. After being treated with saccharin for nine days, the populations of gut bacteria in the mice shifted dramatically and corresponded with an increase in their glycemic index. Specifically, the bacterial group Bacteroidetes increased while the group Clostridiales decreased. These changes in bacterial populations is associated with obesity in mice and people.

When they administered antibiotics to reverse this and return the bacterial populations to a healthy state, it also countered the effects of saccharin, returning glucose levels to normal. To take it a step further, researchers took feces from saccharin-consuming mice showing glucose intolerance and transplanted them into other mice that had never consumed saccharin. Remarkably, those mice started showing signs of glucose intolerance.

In a study of 400 people, those who consumed artificial sweeteners had a gut microbiome that was vastly different from those who did not. They had a group of people consume high levels of artificial sweeteners for seven days, and like the rats their glucose levels increased and their microbiomes changed.

Overall, these studies show that artificial sweeteners may induce glucose intolerance instead of preventing it due to the intimate connection between the bacteria that live in our digestive systems and our metabolic state. In the future, expect to see diagnostic and therapeutic procedures that utilize our microbial friends.

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Sweet Stem Cells

May 11, 2015 by

May 8, 2015

By Medical Discovery News

Stem Cells

Diabetes may be common, but it’s serious business. Diabetes is repeatedly in the top 10 causes of death for Americans, killing or contributing to the deaths of 300,000 Americans in 2010. An estimated one in 10 people have it, but about one-third of them are undiagnosed. Diabetes costs the country $250 billion. But scientists are working on some good news for diabetics with the help of stem cells.

Type 1 diabetes is largely associated with children and represents about 5 percent of all diabetes cases. The more common form, type 2 diabetes, mostly affects adults and manifests when cells do not use insulin effectively so higher levels are needed (also called insulin resistance). Insulin is a molecule of protein, made and secreted by beta cells in the pancreas, an organ that regulates glucose levels in the blood.

Diabetes is a multifaceted disease that leads to a host of medical conditions and complications, such as high blood pressure, elevated cholesterol, blindness, cardiovascular disease, and kidney problems. Those with diabetes are two times more likely to die of a heart attack and one and half times more likely to die of a stroke. Diabetes is the leading cause of kidney failure, leading to transplants and dialysis. Almost 60 percent of lower extremity amputations are the result of diabetes.

Administering insulin is a common treatment for the disease and there are many different forms that can be used. Insulin can be injected by a syringe or delivered via an automated pump. There are also different pharmaceuticals used in oral treatments for diabetes. Biomedical scientists are developing other methods to treat diabetes, such as transferring insulin-producing beta cells from a donated pancreas into a diabetic patient. This works well, but the cells stop working over time. Transplanting a whole pancreas is also an option that relieves the need to administer insulin, but there is always a short supply of donated organs and the possibility that the new body will reject it.

However, recent stem cell experiments by multiple groups working independently show promise. These cells, called S7, produce insulin and regulate the level of glucose in the blood and successfully eliminated diabetes in an animal model in about 40 days. Unlike organ transplants, there is no limit to the supply of these stems cells, no long wait for a donation that’s a good fit, and no need for immunosuppressant drugs.

But the method is not perfect. First, S7 cells react slower to glucose than natural beta cells and do not make as much insulin. There are also questions as to whether this approach could be used to treat Type 1 diabetes, because the insulin-producing cells are destroyed in an autoimmune process, which might destroy the transplanted cells as well.

It’s premature to claim this innovation is a victory over diabetes, but its development will definitely be worth following.

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Chocolate on My Mind

April 25, 2015 by

April 10, 2015

By Medical Discovery News

Chocolate

Peanuts creator Charles Schulz once said, “All you need is love. But a little chocolate now and then doesn’t hurt.” New research shows he might be right. In one study, certain compounds in cocoa called flavanols reversed age-related memory problems.

Flavanols, found in a variety of plants, are potent antioxidants that help cells in the body deal with free radicals. Free radicals arise from normal cellular processes as well as from exposure to environmental contaminants, especially cigarette smoke. Unless your body gets rid of free radicals, they can damage proteins, lipids, and even your genetic information. You can get flavanols from tea, red wine, berries, cocoa, and chocolate. Flavanols are what give cocoa that strong, bitter, and pungent taste. Cocoa is processed through fermentation, alkalization, and roasting among other methods, which can influence how much of the good flavanols are lost. Among the products made from cocoa, those with the highest levels of flavanol are cocoa powders not processed by the Dutch method, followed by unsweetened baking chocolate, dark chocolate and semi-sweet chips, then milk chocolate, and finally chocolate syrup contained the least.

In the latest study, a cocoa drink specially formulated by the Mars food company to retain flavanols was compared with another drink that contained very little flavanols. The study asked 37 randomly selected adults aged 50 to 69 to take one of the drinks. One group consumed 900 milligrams per day of flavanols and the others consumed only 10 milligrams per day for three months. Brain imaging and memory tests were administered before and after the trial.

Those who consumed the high levels of cocoa flavanols had better brain function and improved memories. Before the study, the subjects on average demonstrated the memory of a typical 60-year-old person. At the end, those who consumed more flavanols exhibited the memory capabilities more closely resembling a 30- to 40-year-old. Unfortunately, the average candy bar contains only about 40 milligrams of flavanol, so you would have to eat 23 of them a day to equal the amount of flavanol used in the study, which would lead to other health problems like obesity and diabetes.

Other studies have similarly revealed that high-flavanol cocoa beverages cause regional changes in the brain’s blood flow, suggesting that it could be used to treat vascular impairments within the brain. Flavanols have also been reported to reduce blood pressure and other factors that lead to cardiovascular disease, improve insulin sensitivity, modulate platelet activity thereby reducing the risk of blood clots, and improve the activities of the endothelial cells that line our blood vessels. The Kuna indians living on the San Blas Islands near Panama, who consume a type of cocoa rich in flavanol on a daily basis, have unusually low rates of hypertension, cardiovascular disease, cancer, and diabetes.

These studies need to be repeated with larger groups to confirm the benefits of consuming flavanols and to ensure that there are no negative effects. Still, if a cocoa beverage high in flavanols could be mass produced and marketed, we could improve human health in a very tasty way.

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Vaginal or C-section: Does it matter?

February 22, 2015 by

Feb. 20, 2015

An infant

In the climax of William Shakespeare’s “Macbeth,” the title character is sword fighting and believes himself invincible because he was given a prophesy that said “no man born of woman shall harm thee.” Yet, that is how he was tricked, for his rival, Macduff, was “from his mother’s womb untimely ripped.” This and other historical references show that cesarean sections have been used for centuries, but today the high success rate has made them more common than ever.

The origin of the term Cesarean is popularly and probably falsely attributed to the birth of Julius Caesar. This is unlikely, since C-sections at this time almost always resulted in the death of the mother, and historical records mention Caesar’s mother later in his life. However, the origin may still be linked to Caesar as a law enacted during Caesar’s reign stated that a dead or dying pregnant woman was to be cut open and the child removed from her womb to save the child. Widespread use of this procedure began after anesthetics and antimicrobial therapies became available in the 20th century.

In 1965, 4.5 percent of America’s babies were delivered via C-section. Today that figure has risen to almost one in three, and is on the rise worldwide as well. There are plenty of medical and nonmedical reasons for this shift from vaginal childbirth. Both come with side effects and consequences, some lasting longer than others. For example, C-sections have been linked to increased rates of diabetes and obesity, although we’re not sure why. In a recent study, birth by C-section lead to epigenetic changes in the child’s DNA.

Epigenetics are changes in our DNA that don’t result from changes in our genetic code. These changes can come from environmental factors, such as smoking, that alter the ability of a gene to be seen or expressed. What we didn’t understand until relatively recently is that epigenetic changes can be transmitted to offspring. So you are the product of your parents’ DNA and the environmental factors that affected your DNA in your lifetime and their lifetime before you were born. Then your DNA and epigenetic information is passed on to new generations. These changes accrue and could affect your children or grandchildren. So the descendants of a smoker may inherit more than their name, but epigenetic changes in DNA as well.

New research suggests certain epigenetic changes in a baby’s DNA called methylation are different depending on the type of birth. When DNA becomes methylated, it changes whether a gene is used to make a protein and this can then alter the properties of specific cells. In this study, researchers compared the DNA methylation patterns in stem cells of 25 vaginally delivered babies and 18 delivered by C-section. Distinct methylation changes were seen in more than 300 different regions of the genome between the two groups. Interestingly, many of these regions are associated with genes that control the immune system. We don’t know how these epigenetic changes affect the immune system and ability to fight disease, and don’t have sufficient information to link these differences to later health issues. But this remains an intriguing possibility and awaits more research.

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Sweet Guts

November 29, 2014 by

Nov. 21, 2014

By Medical Discovery News

Sweet guts

Your tongue isn’t the only part your body that can taste sweetness. Three years ago, scientists discovered that our intestines and pancreas have receptors that can sense the sugars glucose and fructose. This could revolutionize treatment for diabetics, who must closely monitor their blood sugar levels. A drug called New-Met, made by Eleclyx Therapeutics in San Diego, that is now in phase II clinical trials is attempting to do just that by targeting those sugar receptors in the digestive system.

It appears these taste receptors are basically sensors for specific chemicals that can serve functions other than taste in other parts of the body, although we don’t know what all those functions are yet. We do know the function of the T1R2/T1R3 taste receptor found on some cells in the intestine. When they detect sugar molecules, these cells secrete hormones called incretins, which in turn stimulate insulin production in the pancreas.

This neatly explains a phenomenon that had mystified scientists for over 50 years: eating glucose triggers significantly more insulin than injecting it directly into the bloodstream. When intestinal cells with sweet receptors detect sugar, they trigger neighboring cells to make a glucose transporter that allows the sugar to be absorbed by the body. The faster sugar is absorbed, the more signals are sent to the pancreas, and the more insulin it releases. Signals are also sent to the brain to tell us we are satiated. Artificial sweeteners can trigger the same effect. Understanding these signals is critically important in the control of blood sugar levels.

Metformin is a drug commonly prescribed to those with type 2 diabetes. It regulates blood sugar levels by decreasing the amount of glucose produced by the liver. Metformin may also modulate multiple components of the incretin signaling system. In combination with insulin, it increases the use of glucose in peripheral tissues like muscles and the liver, especially after meals, reducing blood sugar levels even further. Metformin is usually taken orally, so that it dissolves in the stomach and travels through the bloodstream to the liver.

New-Met is a novel formulation of metformin that dissolves when exposed to the pH in the intestine rather than the stomach. There, it binds to those sweet receptors and activates the release of incretins that stimulate the release of insulin, thereby regulating blood sugar levels. This mimics the natural signaling process triggered by sugars and is fast and direct. This reduces the amount of drug required to be effective by 70 percent. Patients on New-Met had fewer gastrointestinal side effects than those taking the standard metformin, which is the primary reason diabetics choose not to take it.

The number of people with diabetes will soon climb to 592 million, so the demand for better medications to treat them will continue to climb as well.

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A Teaspoon of Agavin

September 13, 2014 by

Sept. 12, 2014

By Medical Discovery News

Agave plant

Next time you have a bitter pill to swallow, think about reaching for a spoonful of agavin instead of sugar to help the medicine go down. You might not know what agavin is yet, but you’ve probably noticed that a number of alternative natural sweeteners like Stevia have been added to grocery store shelves next to traditional sugar. These products sweeten foods but often do not add calories or raise blood sugar levels. Recent research suggests that a sweetener made from agave, the same plant used to make tequila, may lower blood sugar levels and help people maintain a healthy weight.

Agavin is a natural form of sugar, fructose, called fructan. With fructan, individual sugar molecules are linked together in long chains. The human body cannot use this form of fructose, so it is a nondigestible dietary fiber that does not contribute to blood sugar levels. But it can still add sweetness to foods and drinks. Alternatively, agave syrup or nectar, while made from the same plant, contains fructan that has been broken down into individual fructose molecules so it does affect caloric intake and blood sugar levels.

Studies of mice prone to diet-induced obesity and type 2 diabetes found that when they consumed agavin, they ate less and had lower blood glucose levels, increased insulin, and more glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone that inhibits gastrointestinal motility, which causes people to eat less because they feel fuller. It also stimulates the production of insulin. GLP-1 appears to be a regulator of appetite and food intake, and so it is being evaluated as a therapy for type 2 diabetes.

Further testing showed that when agavin was added to the water supply of mice eating a normal diet, they ate less, lost weight, and had lower blood glucose levels compared with mice that consumed other sugars such as glucose, fructose, sucrose, agave syrup, and the artificial sweetener aspartame. While these results are encouraging, the studies need to be replicated and then done using humans for agavin’s effectiveness to be proven. The possible long-term consequences of its use must also be examined. So far, the only known down sides are that agavin is not yet widely available and that it is not as sweet as sucrose or artificial sweeteners.

Agavin would join other natural sweeteners that do not add calories or affect blood sugar such as stevia, which is currently found in a variety of products. The stevia plant is native to Paraguay, where its leaves have been used as a sweetener for over a century. Stevia has been the subject of biological and toxicological studies for more than 50 years and its safety is well-established. It stimulates the pancreas to secrete insulin, a benefit to diabetics, and does not alter the naturally-occurring, beneficial bacteria in the digestive tract.

Thanks to agavin and other natural sweeteners, people with diabetes (or anyone watching their caloric and sugar intake) now have more choices than ever for sweeteners and products made with them, so they can eat or drink without raising their blood sugar levels. Agavin: it’s not just for tequila anymore.

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Bear-ly Understanding Diabetes

May 30, 2014 by

May 30, 2014

By Medical Discovery News

What can studying grizzly bears reveal about human diabetes?

While they are some of the largest bears on earth, Grizzly bears aren’t usually accused of being fat. Regardless, these animals are helping scientists discover new and better treatments for human obesity and diabetes.

Grizzlies spend the late summers consuming more than 50,000 calories per day. As a comparison, a moderately active 50-year-old human female is recommended 2,300. Grizzlies then hibernate for up to seven months, relying on the pounds of stored fat they accumulated before winter. While hibernating, bears do not eat, urinate, or defecate. 

Scientists wondered if all the weight and fat bears gain results in diabetes like it does in humans. Overweight people face an increased risk of type 2 diabetes, in which the body does not make enough of the hormone insulin or cells do not respond to it. Insulin helps move a type of sugar called glucose from the blood into cells, where it is used for energy and as a precursor for other molecules the body needs. If sugar levels in the blood remain elevated and the body doesn’t have enough insulin, cells are starved for energy, leading to damaged eyes, kidneys, nerves, and hearts. 

Interestingly, Grizzly bears can actually control their insulin responsiveness. When they are the fattest, they are most sensitive to insulin, thereby keeping their blood sugar levels healthy. Soon after going into hibernation, they switch to complete insulin resistance, meaning they develop type 2 diabetes. But unlike humans, their blood sugar levels remain normal. When they awaken in the spring, their insulin responsiveness is restored. Bears do this not so much to regulate their blood sugar levels as to regulate their storage and utilization of fat. So how do bears control their insulin responsiveness? And could it lead to new treatments for type 2 diabetes in humans?

PTEN is a protein that regulates cells’ sensitivity to insulin. Scientists know exactly when Grizzlies increase or decrease PTEN activity, they just don’t know how. People with a PTEN mutation have a metabolism similar to Grizzlies’.  These people have an increased risk of obesity and cancer but a decreased risk of developing type 2 diabetes because they are more sensitive to insulin.

Grizzlies have also evolved to the ability to accumulate large amounts of fat only in their adipose tissue, just below the skin so it doesn’t interfere with the rest of their bodies. In humans, on the other hand, fat can accumulate in many places like the liver, in muscles, and around other internal organs, which are all highly unhealthy places to keep fat. Bears can also have elevated levels of cholesterol without the serious consequences of cardiovascular disease.

During hibernation, the Grizzly bears’ kidneys shut down. But despite the high levels of toxins that accumulate in the blood without working kidneys, they don’t die or even suffer from it like a human would. When they wake up, their kidney function is restored with no permanent damage.

After millions of years of evolution, Grizzly bears and other animals have developed solutions for biological challenges humans still face. Studying them is a new approach that has the potential to create treatments for many human conditions.

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How Much Sugar Is Safe?

January 31, 2014 by

Jan. 31, 2014

By Medical Discovery News

Sugar

Former Mayor Michael Bloomberg of New York City caused a controversy when he tried to ban the sale of sugary drinks more than 16 ounces. Thus the “Big Gulp” rebellion was born and the ban was later overturned by the courts. Yet the rates of diabetes, heart disease, and obesity remain out of control in the U.S.

In the U.S., 24 million people over age 20 have diabetes. Another 78 million have pre-diabetes with blood glucose levels higher than they should be – the start of glucose intolerance.  And down the road, this may lead to life-threatening heart disease (the No. 1 killer of adults), which is also linked to obesity affecting more than 80 million Americans.

Much of the obesity epidemic has been blamed on unhealthy eating and poor nutrition. Refined sugar has been identified as a source of excess calories. According to the U.S. Departments of Agriculture and Health and Human Services, almost 50 percent of sugar in the diets of Americans comes from sugary drinks and sweetened fruit drinks. The debate over just how much sugar is too much in terms of our health was addressed by a recent study and the results are sending shock waves through the medical community. 

In the experiment, one group of mice ate a normal diet and another group ate a diet where one quarter of the calories came from sugar similar to that in high fructose corn syrup. This level of sugar is pretty equal to that consumed naturally by 15 to 25 percent of the U.S. population. This is equivalent to a person consuming three cans of a sugary beverage a day in an otherwise sugar-free diet. Current nutrition guidelines consider this to be at the top of the safe level of sugar for people.

After 26 weeks of a monitored diet, all the mice were released into an experimental natural environment. Over the next 32 weeks, twice as many sugar-fed female mice died compared to the control group. The sugar-fed male mice produced 25 percent fewer offspring and held 26 percent less territory than mice from the control group. Overall, dietary sugar was linked to a shorter life span, limited reproduction, and lowered competitive success. 

Metabolic measurements on the sugar-fed mice showed changes in glucose clearance and increases in cholesterol levels, but these were considered minor. Nevertheless, life outcomes called Organismal Performance Assays were significantly affected. This may represent a new way to gauge important changes in overall life parameters without corresponding physiological changes.

This certainly raises the question of how much sugar is too much, and the debate over the appropriate level of refined sugar for good human nutrition will continue. It will be interesting to watch in the coming months and years to see if these results are substantiated and if they lead to new nutritional guidelines. Who knows – maybe Mayor Bloomberg was right after all!

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Insulin by Nanoparticle

November 22, 2013 by

Nov. 22, 2013

By Medical Discovery News

Diabetes is a life-changing diagnosis that can mean several injections of insulin and several tests of blood glucose levels every day. Some people with diabetes say they feel like a pin cushion, and children with Type 1 diabetes often find it particularly challenging. However, there may be some relief in sight thanks to nanoparticles.

Researchers have developed a new insulin delivery system that involves a network of nanoparticles. Nanoparticles range in size from one to 2,500 nanometers. For an idea, the width of a strand of human hair is 100,000 nanometers. Once injected, the nanoparticles release insulin in response to increases in blood sugar levels for up to a week. They have been tested in mice and if they perform similarly in people, this may be a better solution than multiple daily injections.

Nanoparticles used to deliver insulin consist of an insulin core, modified dextran, and glucose oxidase enzymes. When glucose levels rise in the blood, the glucose oxidase enzyme in the nanoparticle activates and converts the blood glucose into gluconic acid. This in turn dissolves the modified dextran, releasing the insulin in the core of the nanoparticle.

The more sugar in the blood system, the more insulin is released, mimicking what the pancreas does in those without diabetes. Insulin is a hormone produced by the pancreas that is required to get glucose into cells.

Those with Type 1 diabetes must estimate the amount of carbohydrates in the foods they intend to eat, test their blood sugar levels, and then calculate the amount of insulin that will hopefully keep them in the normal range. The body uses carbohydrates to make glucose, which is the primary fuel for cells. Carbohydrates include simple sugars like lactose, fructose, and glucose that are found naturally in foods such as milk, fruits, and vegetables. However, natural and artificial sugars like corn syrup, sweeteners, and dextrose are also added to many processed foods. Everyone, especially diabetics, is encouraged to limit foods that are high in added sugars.

Complex carbohydrates such as starch and dietary fiber are broken down to glucose but much more slowly. Dietary fibers are in vegetables, fruits, beans, peas, and whole grains. Most Americans don’t get enough dietary fiber because they eat too much bread and dough made from refined flour. Most people, including diabetics, benefit from increasing the amount of whole grains such as brown rice, quinoa, whole wheat, rye, and oats they eat. 

According to the American Diabetes Association, in 2011 there were 25.8 million diabetics, 8.3 percent of the population. An estimated 7 million more have not been diagnosed and another 79 million are prediabetic. In 2012, treating diabetes cost $245 billion.

While it is also important to control the number of new cases of diabetes, devising new methods to more precisely control blood sugar will reduce complications from diabetes and make the lives of diabetics easier.

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An Itchy Situation

November 2, 2013 by

Nov. 1, 2013

By Medical Discovery News

Anyone ever bitten by a mosquito can attest to its itchy consequences. New research has discovered just how our bodies detect and process itching, leading to a better understanding of our reaction to itching and hopefully better treatments for it.

The clinical term for an itch is pruritus, and at least 16 percent of people experience an itch that just doesn’t go away. The most common dermatological complaint, long-term itching can be caused by chronic renal disease, cirrhosis, some cancers, multiple sclerosis, diabetes, shingles, allergic reactions, drug reactions, and pregnancy.

Prolonged itching and scratching can increase the intensity of the itch, possibly leading to neurodermatitis, a condition in which a frequently scratched area of skin becomes thick and leathery. The patches can be raw, red, or darker than the rest of the skin. Persistent scratching can also lead to a bacterial skin infection, permanent scars, or changes in skin color. The super strong pain reliever morphine can cause such a severe whole-body itch that some patients choose to forgo it and live with the pain.

Sensory neurons called TRPV1 cells detect itchy substances on skin. TRPV1 cells have long nerve fibers that extend into skin, muscle, and other tissues to help monitor conditions. It has not been clear how these neurons sort through different sensations like pain and temperature and route the signal along the proper pathway to the appropriate area of the brain for perception.

New research has revealed a small group of those neurons produce a substance called natriuretic polypeptide b (Nppb), a hormone known to be involved in regulating the heart. Surprisingly, when Nppb is produced by TRPV1 cells it acts as a neurotransmitter, a chemical messenger secreted by neurons to carry, boost, and control signals between neurons and other cells.

When scientists genetically modified mice to eliminate Nppb, they did not itch. Nppb binds to a specific receptor called Npra on particular nerves in the spinal column. When those cells were eliminated in mice, again, they did not itch. Interestingly, removing these cells did not impact other sensory sensations such as temperature, pain, and touch.

A similar transmission presumably exists in humans, but that has not yet been determined. Knowing which molecules and cells are involved will help scientists study how humans perceive itch signals. Before these findings, scientists thought a molecule called gastrin releasing peptide was responsible for transmitting the itch signal from nerves, and that itching was a low level form of pain.

Understanding the itch signaling pathway offers the opportunity to create drugs that specifically block that signal and alleviate unpleasant and chronic itching with fewer side effects.

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