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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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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The Trouble with Sugar Substitutes

December 20, 2013 by

Dec. 20, 2013

By Medical Discovery News

Those reaching for a packet of artificial sweetener to satisfy a sweet tooth without adding calories may want to think again – the long-time diet staple may actually lead to serious unintended side effects.

Artificial sweeteners include the recently launched Stevia products like Truvia and the compounds  aspartame (found in Equal), saccharin (Sweet N’ Low), and sucralose (Splenda). These were developed because they add no caloric content to the foods they are added to, but they stimulate the sweet receptors on the tongue. Non-caloric sweeteners are popular with those working to control their weight because of the allure of no calories without sacrificing sweetness.

Consider one product – yogurt. There can be 200 calories or more in those sweetened with sugar while the artificially sweetened varieties come in under 100 calories. The shine of artificial sweeteners may be wearing off though, as some recent studies suggest their use may actually lead to weight gain.

The first sign that artificial sweeteners weren’t as harmless as they seem was a study in the 1970s that linked saccharin to bladder cancer, although those results aren’t substantiated, and approved artificial sweeteners are now considered generally safe for human consumption.

In a new study at Washington University in St. Louis, scientists looked at people with a body mass index (BMI) of over 42 (30 and over is considered obese), who don’t have diabetes and don’t regularly use sweeteners. Individuals were divided into two groups and given the artificial sweetener sucralose or water before ingesting a solution of glucose, the same amount given during a glucose tolerance test. On a separate day, the groups were reversed so researchers could compare the effects in each person.  

The results were surprising. When individuals drank sucralose before ingesting glucose, their insulin levels peaked at a higher level and increased by about 20 percent more than those drinking water alone. This means that sucralose was affecting insulin and blood glucose levels. Previously, scientists thought that these sweeteners did not have an effect on sugar metabolism. 

It turns out that there are sweet responsive receptors in the gut and pancreas that are similar to those found on the human tongue. When they are stimulated, they can cause an increase in the release of hormones including insulin. This in turn causes more sugar to be absorbed in the gut and subsequently higher levels in the blood. For unknown reasons, it happens only in the obese. An elevation in insulin levels can contribute to insulin resistance and type 2 diabetes. 

One thing is for sure – further research will help scientists understand the effects of artificial sweeteners on human metabolism.

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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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Weight-Loss Surgery Can Treat Diabetes

August 4, 2011 by

Woman went from having five shots a day to none

By Pamela Bond

Victoria Advocate

March 25, 2008

Windy Slone, a diabetic for eight years, took her last insulin shot on Dec. 19. A few days later, doctors told her she was free of diabetes. About one month later, she no longer needed the five other medications she’d been taking.

“I went from having five shots a day for the past four years to none. It’s amazing,” Slone said. “Three weeks ago I gave all my unused syringes to my friends and my family had a drumroll around the trash can as I threw the rest away.”

Slone, a 34-year-old mother of two who lives in Rockport and works for the Holiday Beach Homeowner’s Association, underwent gastric bypass surgery at Citizens’ Bariatric Center on Dec. 18. Like 90 percent of patients who have Type 2 diabetes at the time of surgery at the center, the disease disappeared after the operation, said Dr. B. Dean McDaniel of the center. Most patients stay in the hospital for one or two days and return to work after a week or two.

In gastric band surgery, when a lap band is placed around the opening of the stomach, the highest incidence of diabetes in remission occurs two years after the surgery. In gastric bypass surgery, when the stomach is stapled to make it smaller and then the intestines are reconnected to a different opening in the smaller stomach, the effects are immediate because food is re-routed away from the pancreas.

Slone has lost 60 pounds and McDaniel predicts she will lose a total of 100 pounds by the end of the year. Besides losing weight and no longer having diabetes, Slone said the best effect of the surgery is having more energy.

“My youngest said, ‘Mom, I love your energy, but you’re scaring me,'” Slone said. “I can’t wait to play chase with my daughters and I’m excited that when we go camping and hiking, I’ll get to go with them instead of watching.”

After the surgery, Slone could only eat soft foods in small portions. After her six-week check-up, doctors allowed her to eat regular food again, but still in small portions.

“It was an adjustment, but it’s worth it,” Slone said. “I’ve only been sick from eating something once. People ask me if I feel hungry, if I have cravings. I don’t. I eat for nourishment now. I eat to survive. I stop when I’m full.”

Requirements for gastric bypass or band surgery in the United States are still tied to obesity and not diabetes, McDaniel said, but a study being conducted in other countries will see if the surgery yields similar results when it is modified for patients who want to lose the disease and not the weight.

Both surgeries are becoming more common and insurance companies are covering more of them, McDaniel said.

“Every year we have more inquiries,” McDaniel said. “People are seeing a decrease in complications, an increase in security. Insurance companies are slowly seeing the financial benefits.”

Slone said her advice to anyone going through weight-loss surgery is to follow your doctor’s instructions and don’t push your limits.

“For any diabetic thinking abou this procedure, it’s a miracle,” Slone said. “It’s a blessing. I tell everyone about it. If I can convince one person on the edge to do this, I’ll feel like I’ve accomplished something.”

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