Sweet Guts

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 Whiff of Flavor

By Medical Discovery News

June 30, 2012

Most would agree that the best part of eating is the flavor and taste of food. But what is the difference between flavor and taste? Not everyone can appreciate the difference between them.

The truth is, even for scientists, taste is easier to explain. That’s partly because taste is definitive and limited to five types: sweet, sour, bitter, salty and umami, otherwise known as savory.  People detect these different tastes when molecules from food bind with receptors on the tongue.

Flavor, by contrast, is more complex, and scientists are now learning that flavor’s role in the human brain is powerful. Rather than being sensed by tastebuds, flavor is actually experienced in the brain, and the sense of smell is the key component. A recent book called “Neurogastronomy” by Gordon Shephard, a neurobiology professor at the Yale School of Medicine, focuses on this subject. He explores how the brain’s perception of flavor impacts eating habits such as food preferences and cravings. Flavor presents food in its full dimension, which is why the smell of popcorn makes a person’s mouth water while evoking good memories at the same time. As enjoyable as that may be, the downside of flavor is people make poor food choices, contributing to today’s high obesity rates.

Years of research are helping scientists understand how flavor works. It’s created by the sense of smell. When a person chews and swallows, they’re also breathing. The process of inhaling pulls chemicals released by food into the nasal cavity where they are detected by sensors.  This is called “retrosmell.”  When these signals are transmitted to the brain, a spatial pattern is created. That means the brain creates a smell image, just as a visual image is formed from what is seen.

From there, flavor can further engage the brain by interacting with higher, cognitive regions that control emotion and memory, creating more excitement for or reward from food.  Shepard believes flavor’s role in the brain has an impact on modern social, behavioral and medical issues – particularly on the challenges many people face in making healthy food choices.

If flavor indeed plays such a large role, it goes against a school of thought among evolutionary biologists that the sense of smell has waned. Early research shows as primates evolved into humans, the number of functional olfactory receptor genes declined.  But recent studies, including Shepard’s book, argue people make up for the loss of receptors with retronasal smell, olfactory brain areas, and language. If human smell perception is better than previously thought, it may have been quite important in human evolution.  Its significance continues to play out. After all, who can resist their favorite treats?

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Berry Berry Good

By Medical Discovery News

June 2, 2012

Synsepalum dulcificum

As intriguing as its name is, the Miracle Berry’s effect on the tongue is even more fascinating. Minutes after popping the luscious red berry in the mouth and swirling its pulp around, a shot of Tabasco sauce will suddenly taste like spicy doughnut glaze.

The magical little fruit changes the way taste buds perceive certain flavors, especially sour, acidic foods. The cranberry-sized fruit comes from a plant called Synsepalum dulcificum native to West Africa where people have enjoyed its properties for centuries. Yet, until recently, no one knew why it is able to change the taste of sour foods into deliciously sweet treats.

Forty years ago, scientists discovered a protein appropriately named miraculin is the active ingredient in the berry. Though they couldn’t be sure, scientists guessed the protein binds to sweet taste receptors on the tongue, changing the way sour foods taste. A study led in part by Ayako Koizumi from the University of Tokyo not only confirmed this hunch, but uncovered the specifics of the protein’s mechanisms.

Though its chemical properties make miraculin a super sweetener, unlike others, miraculin does not trigger the sweet receptors on its own. In fact, the Miracle Berry has the unremarkable taste of a mild cranberry. Once spread around the mouth, its proteins bind with taste receptors on the tongue, which are bundled into clusters of 50 to 100 to form taste buds.  The Tokyo study found that compared to other sweeteners, miraculin binds to receptors more strongly and changes the shape of receptors so that other sweeteners can’t latch on. That’s why aspartame tastes bland after eating a Miracle Berry.

However, when an acid is introduced in the mouth, the sweetness goes through the roof because miraculin itself changes shape by attracting extra protons. This supercharges the sweet receptors, so that oysters with lemon juice taste like chewing gum. Lemon sorbet with Guinness tastes like a chocolate milkshake.  And something sweet can taste too sweet or cloying. Once the sour food is swallowed, miraculin changes back to its original shape, waiting for the next acid to come along.

The effect of a Miracle Berry lasts about an hour or sometimes two, but the fruit is expensive at $2 a piece. Its popularity has attracted companies to extract miraculin, purify it, and sell it in tablet form, which works the same way. Although the berry and tablet are available on the Internet, the Food and Drug Administration reviewed but did not approve miraculin as a sugar substitute in the 1970s. Now various groups are petitioning to change this ruling, which they believe was influenced by special interests.

Without a means for wide commercialization, the fruit has become the focus of taste-tripping parties where people pay to try the fruit with everything from goat cheese to beer.  But it’s also found a higher calling. For cancer patients whose chemotherapy treatments leave a metallic taste in their mouths, the Miracle Berry can make eating pleasurable again.

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