Treatment For Gastrointestinal Conditions May Be Improved By Targeting Neurotransmitter

Selective targeting of the neurotransmitter that differentially affects brain cells that control the two distinct functions of the pancreas may allow for new medication therapies for conditions like diabetes, dyspepsia and gastro-esophageal reflux, according to Penn State College of Medicine researchers.
"This study differs from what's been reported

previously about brain neurons that control the gastrointestinal tract," said R. Alberto Travagli, professor, Department of Neural and Behavioral Sciences, and lead investigator. "It provides further support to the idea that separate nerve pathways regulate the diverse functions of organs along the upper gastrointestinal tract."
The pancreas has two functional parts: one that releases digestive enzymes, and one that releases hormones like insulin and glucagon. The vagus nerve, which originates in the brain, regulates both of these pancreatic functions. This nerve detects chemical and biological changes that occur along the gastrointestinal tract and interprets and integrates these signals before sending appropriate responses back to the organs. In the brain, these signals tell the nerves controlling each specific organ what the proper response is -- for example, digestive processes and insulin release -- according to the signals detected in the GI tract.
Neurotransmitters in the brain and in organs like the pancreas control the nerve networks that receive these signals. Neurotransmitters are chemicals released from nerves that allow them to communicate with each other as well as with organs of the body. One of these neurotransmitters is glutamate, which acts on specific proteins called receptors that are present on the nerve cells. There are different classes and types of receptors that glutamate can act upon; one major class of these receptors is metabotropic glutamate receptors (mGluRs). This class is further divided into three subgroups -- I, II or III -- depending on their location and function on the nerve cells.
"The aim of this study was to investigate how these mGluRs are organized on nerve synapses -- the specialized structures that allow a signal to pass from one cell to another cell," Travagli said. "The second aim of the study was to see whether pancreatic insulin and enzyme secretions are controlled by different types of vagal motoneurons -- the cells of the nervous system that control motor functions of the pancreas through the vagus nerve."
Group II and III mGluRs are present in synapses that can either excite or inhibit the vagal nerve cells that send signals to the pancreas, and different outcomes can be seen depending on which group of mGluRs glutamate acts upon. When glutamate acts upon either group II or group III mGluR, insulin secretion is decreased. Pancreatic enzyme secretion is increased only by activation of group II mGluR by glutamate.
"The data shows mGluRs on brainstem vagal nerve circuits that regulate pancreatic functions are organized in a very specific manner," Travagli said. "This type of separation in their organization may allow for development of selective drugs that target very specific vagal neurocircuits in patients with such conditions as gastrointestinal reflux disorders, functional dyspepsia, gastroparesis and pancreatic exocrine or endocrine dysfunctions."

Related articles

• Treatment For Gastrointestinal Conditions May Be Improved By Targeting Neurotransmitter (medicalnewstoday.com)
• In T2 Diabetes, Which Comes First: High Insulin Levels or Insulin Resistance? (diabeticmediterraneandiet.com)
• Targeting neurotransmitter may help treat gastrointestinal conditions (sciencedaily.com)

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Pig That Models Human Diseases Such As Obesity, Diabetes, And Cardiovascular Disease Gets International Attention

A detailed annotation of the genome of T.J. Tabasco, a pig from the University of Illinois South Farms, is the outcome of over 10 years of work by an international consortium. It is expected to speed progress in both biomedical and agricultural research. U of I Vice President for Research Lawrence Schook said that the College of ACES played a crucial role in getting the work started.

Funding that came through ACES allowed Schook and others to put together the Swine Genome Sequencing Consortium, an alliance of university, industry, and government laboratories in the U.S., Europe, and Asia. The USDA committed 10 million dollars to the project. Today the project includes scientists from more than 50 research groups.
Schook said that the project has three main objectives: (1) to serve as a blueprint for understanding evolution and domestication, (2) to advance research on animal production and health, and (3) to explore ways to use the pig in biomedical applications.
The first publication, which just appeared in Nature, focuses on the pig's evolution. Researchers compared the reference genome from T.J. Tabasco with genomes of wild and domestic pigs from Europe and Asia (including archaeological and museum samples), and to human, mouse, dog, horse, and cow genomes.
"The pig is interesting because the wild boar still exists," Schook explained. "We could look at domestication, and we also looked at speciation. From an evolutionary perspective, these Sus species diverge in a very short time."
The researchers traced the domestic pig back to Southeast Asia. From there, it spread across Eurasia. The glaciation period separated the pigs into two groups about one million years ago. Today they are almost sub-species. "However, their chromosome structures have stayed very similar," Schook noted.
Pigs were independently domesticated in western Eurasia and East Asia 10,000 to 15,000 years ago. There is evidence that as the early European settlers moved around, they bred the domesticated females with wild boars.
Pigs in Central and South America are thought to have originated on the Iberian Peninsula. In a paper soon to be published in Heredity, the researchers tracked how these pigs adapted to different climates, altitudes, and diets.
As well as providing insights into how the pig evolved, the genome sequencing provides valuable new tools for animal breeding. One is a DNA test that can identify individual pigs that are less susceptible to certain diseases or have a genetic predisposition to fattening rapidly, eating less, and bearing many offspring.
On the biomedical side, researchers will build on ongoing efforts to use the pig to model human diseases, including lifestyle diseases such as obesity, diabetes, and cardiovascular disease. The sequencing identified 112 genes in pigs that are also responsible for diseases in people, suggesting that pigs could be used for drug testing.
Another direction is to use pigs as a source of organs for humans. Schook mentioned islet cells for diabetics as an example.
"Human transplant of eyelets doesn't work because there's not enough cells in a single pancreas," he explained. "If you could have an animal source, even if they get rejected, they're plentiful."
Clearly, there are a plenitude of exciting possibilities for future research. "For me, the next phase is looking at this concept of epigenomics - of how the environment affects gene expression," Schook said.

Related articles

• Scientists Sequence Entire Pig Genome in Breakthrough That Could Combat Human Disease (medicaldaily.com)
• Pig genome helps us understand why they eat crappy things (southofheaven.typepad.com)
• Pig That Models Human Diseases Such As Obesity, Diabetes, And Cardiovascular Disease Gets International Attention (medicalnewstoday.com)

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Increased Risk For Diabetes When Obesity And Low Vitamin D Are Present

The combination of obesity and vitamin D deficiency may put people at even greater risk of insulin resistance than either factor alone, according to new research from the Drexel University School of Public Health recently published early online in the journal Diabetes Care. Insulin resistance is a major risk factor for Type 2 diabetes, a condition that affects 25.6 million adults and is the seventh leading cause of death in the United States.
"Vitamin D insufficiency and obesity are individual risk factors for insulin resistance and diabetes," said lead author Shaum Kabadi, a doctoral candidate in epidemiology at Drexel. "Our results suggest that the combination of these two factors increases the odds of insulin resistance to an even greater degree than would have been expected based on their individual contributions."
In the study, obese individuals who had healthy levels of vitamin D had insulin resistance almost 20 times more often than the overall study population. But in obese individuals whose serum vitamin D was low, insulin resistance was much higher: about 32 times more common than the average.
Senior author Dr. Longjian Liu, an associate professor in the School of Public Health, noted, "It's not clear whether obesity itself causes a low vitamin D level or if it's the other way around."
Vitamin D is stored in adipose fat tissues, making it unavailable for the body to use; as a result, people who are overweight are already more likely to have low levels of serum vitamin D. Vitamin D deficiency is associated with multiple health conditions including diabetes, cardiovascular diseases including stroke, depression, dementia and other conditions.
Kabadi, Liu and co-author Dr. Brian Lee, an assistant professor in the School of Public Health, analyzed data on serum vitamin D levels and indicators of insulin resistance and diabetes from 5,806 respondents to a major national health survey, the National Health and Nutrition Examination Survey (NHANES). This was the first study of the association between vitamin D and diabetes risk for obese patients using a large, nationally representative sample of adults. The survey reported data from individuals at a single point in time and was therefore unable to determine whether there is a cause-and-effect relationship among vitamin D, obesity and insulin resistance.
Further studies could indicate whether vitamin D supplements are effective at reducing the risk of insulin resistance and diabetes in obese individuals. If so, the authors noted that it would be an inexpensive and practical prevention strategy compared to the difficulty involved in healthy weight loss.
Liu said that vitamin D supplements may be useful for people who are overweight or obese to help control diabetes, but he cautioned that too much vitamin D can cause side effects such as weakness and fatigue. In addition, vitamin D deficiency is just one of many known risk factors associated with insulin resistance and diabetes. "Therefore, to control diabetes, we need to have comprehensive prevention strategies. For example, physical activity may be the most cost-effective way to control weight and subsequently to control conditions including diabetes and heart disease," Liu said.

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Waist Size, Regardless Of BMI, Linked To Diabetes Risk

Waist circumference is strongly and independently linked to diabetes type two risk, even after accounting for body mass index (BMI), and should be measured more widely for estimating risk, researchers from the Medical Research Council (MRC) Epidemiology Unit, UK, reported in PLoS Medicine. The authors explained that overweight people with a large waist, over 102cm (40.2 inches) for men and over 88cm (34.6 inches) for women, have approximately the same or higher risk of eventually developing diabetes type 2 as obese individuals.
Dr Claudia Langenberg and team gathered data on over 340,000 individuals from eight European countries to determine what their future risk of developing diabetes type 2 might be.
Dr Claudia Langenberg, said:

"Type 2 diabetes is a serious and increasingly common disease. More than a third of the UK adult population is overweight and at increased risk of diabetes, but they are not systematically monitored for this risk. Our findings suggest that if their waist circumference is large, they are just as likely to develop the condition as if they were obese.
We do not suggest replacing BMI as a core health indicator, but our results show that measuring waist size in overweight patients allows doctors to 'zoom in' on this large population group and identify those at highest risk of diabetes. These people can then be offered lifestyle advice, which can reduce their risk of developing the disease."

Diabetes type 2 is a long-term condition that occurs when the person's body cannot produce enough insulin, or when the cells in the body do not react properly to insulin. The exact causes of type 2 diabetes are not precisely understood, but experts say that being obese or overweight are the main modifiable risk factors.
Langenberg and team set out to determine what the link between BMI, waist size and the likelihood of developing diabetes type 2 might be - they also aimed to find out what the risks were separately for men and women. They gathered data from the European Union funded InterAct Study, consisting of 12,403 individuals with diabetes type 2 who had developed the disease during a 15-year follow up.
They found that:

Overweight people with large waists have the same or higher risks of eventually developing type 2 diabetes as obese individuals

• 7% of males with a large waist who were overweight eventually developed diabetes type 2 within ten years
• 4% of females with a large waist who were overweight eventually developed diabetes type 2 within ten years
• Large-waisted overweight men and women were found to have either the same or higher risk of eventually developing diabetes type 2, compared to obese individuals
• Normal weight men with a small waist had only a 1.6% chance of developing the disease
• Normal weight women with a small waist had a 0.6% risk of developing the disease
• Pear-shaped people - those who were overweight but had a small waist - were found to have a relatively low risk of developing diabetes type 2
• Women with a BMI greater than 35 (obese women) with a large waist were nearly 32-times more likely to eventually develop diabetes type 2 compared to thin women with a small waist
• Obese men with a large waists were 22-times more likely to develop the disease compare to their lean and small-waisted counterparts

Principal Investigator of the InterAct Study, Professor Nick Wareham, said:

"This is one of the most comprehensive studies of lifestyle and diabetes risk to date, not just in scale, but in the powerful prospective design which allows us to follow a population over a long period of time to see how and why disease develops. The results of this important research will help inform new strategies for the prevention of this devastating condition that affects almost three million people in the UK."

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Peaches, Plums, Nectarines Give Obesity, Diabetes Slim Chance

Peaches, plums and nectarines have bioactive compounds that can potentially fight-off obesity-related diabetes and cardiovascular disease, according to new studies by Texas AgriLife Research.

The study, which will be presented at the American Chemical Society in Philadelphia next August, showed that the compounds in stone fruits could be a weapon against "metabolic syndrome," in which obesity and inflammation lead to serious health issues, according to Dr. Luis Cisneros-Zevallos, AgriLife Research food scientist.

"In recent years obesity has become a major concern in society due to the health problems associated to it," said Cisneros-Zevallos, who also is an associate professor at Texas A&M University. "In the U.S., statistics show that around 30 percent of the population is overweight or obese, and these cases are increasing every year in alarming numbers."

While he acknowledged that lifestyle, genetic predisposition and diet play a major role in one's tendency toward obesity, "the major concern about obesity is the associated disease known as metabolic syndrome.

"Our studies have shown that stone fruits -- peaches, plums and nectarines -- have bioactive compounds that can potentially fight the syndrome," Cisneros-Zevallos said. "Our work indicates that phenolic compounds present in these fruits have anti-obesity, anti-inflammatory and anti-diabetic properties in different cell lines and may also reduce the oxidation of bad cholesterol LDL which is associated to cardiovascular disease."

What is unique to these fruits, he said, is that their mixture of the bioactive compounds work simultaneously within the different components of the disease.

"Our work shows that the four major phenolic groups -- anthocyanins, clorogenic acids, quercetin derivatives and catechins -- work on different cells -- fat cells, macrophages and vascular endothelial cells," he explained. "They modulate different expressions of genes and proteins depending on the type of compound.

"However, at the same time, all of them are working simultaneously in different fronts against the components of the disease, including obesity, inflammation, diabetes and cardiovascular disease," he explained.

Cisneros-Zevallos said this is believed to be the first time that "bioactive compounds of a fruit have been shown to potentially work in different fronts against a disease."

"Each of these stone fruits contain similar phenolic groups but in differing proportions so all of them are a good source of health promoting compounds and may complement each other," he said, adding that his team plans to continue studying the role of each type of compound on the molecular mechanisms and confirm the work with mice studies.

The studies on the health benefits of stone fruit are funded by the California Tree Fruit Agreement, The California Plum Board, the California Grape and Tree Fruit League and the Texas Department of Agriculture. The Cisneros-Zevallos lab team in this study included Freddy Ibanez, Paula Castillo, Paula Simons and Dr. Congmei Cao.

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No Association Found Between White Potato Consumption (Baked, Boiled Mashed) And Obesity, Type 2 Diabetes Or Systemic Inflammation

Preliminary Research presented at The Federation of American Societies for Experimental Biology (FASEB) Conference in San Diego demonstrates that habitual consumption of white potatoes (baked, boiled and mashed) is not associated withobesity, type 2 diabetes or levels of C-reactive protein, a marker of systemic inflammation once potential confounding factors are controlled for (e.g., age, gender, and education). Previous studies examining the association between potato consumption and disease states have failed to consider demographic factors that could potentially confound the relationships such as age, gender, race/ethnicity, and education. "One of the purposes of this study was that we hypothesized demographic factors - particularly socioeconomic status - might be associated with both potato consumption and the prevalence of obesity and diabetes. Therefore we controlled for these factors," said lead researcher Adam Drewnowski, PhD, Professor of Epidemiology and Director of the Nutritional Sciences Program at the University of Washington.
Dr. Drewnowski and colleagues examined dietary intake and health data in a representative sample of 5,800 adults using two cycles (2003-2004 and 2005-2006) of the National Health and Nutrition Examination Survey (NHANES). After controlling for demographic variables, the researchers found no association between the frequency of potato consumption and obesity, diabetes or C-reactive protein.
Dr. Drewnowski and colleagues further analyzed the NHANES survey data to look at different potato preparations in Americans' diet including French fries, home fries, tater tots, chips, baked, mashed, boiled and salad. They found that although Americans may eat fried potatoes at restaurants, relatively few Americans were preparing fried potatoes at home: only 26% of fried potato servings were sourced from the grocery store.

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Health expert recommends fat tax on unhealthy foods in the UK

The director of the health promotion research group at the University of Oxford has recommended the introduction of a tax on unhealthy foods to help reduce the number of overweight and obese people in the UK.
Mike Rayner has proposed a tax on a range of less healthy foodstuffs, including a 12p ($0.19 4/10) tax on soft drinks to get people to switch to a healthier alternative, as so many people in Britain are obese – which he claims is costing the NHS billions of pounds each year. He argued that since tax increases were already used to deter people from  smoking and drinking, a fat tax would improve our health and help raise money for the Treasury.
Rayner commented "There's evidence to show that manipulating food prices can encourage healthy eating. So why are we so reluctant to change the way we tax food?
He added "We need to rethink the way we apply VAT to food. At the moment we have a muddled system: you do pay tax on some relatively-healthy things like smoothies, but you don't pay it on a lot of junk food like chips or doughnuts." He also pointed out that Denmark already has a "fat tax" on foodstuffs that contain saturated fats, which are known to raise cholesterol levels.
However, the idea was been countered by Labour MP Angela Eagle and the Liberal Democrat minister Steve Webb, who would instead prefer improved nutritional education and better packaging.

We here in America have something similar to the UK Fat Tax called a Sin Tax. A sin tax is a kind of sumptuary tax: a tax specifically levied on certain generally socially proscribed goods and services. These goods are usually alcohol and tobacco, but also include candies, soft drinks, fat foods and coffee, while services range from prostitution to gambling.

Sumptuary taxes are ostensibly used for reducing transactions involving something that society considers undesirable, and is thus a kind of sumptuary law. Sin tax is used for taxes on activities that are considered socially undesirable. Common targets of sumptuary taxes are alcohol and tobacco, gambling, and vehicles emitting excessive pollutants. Sumptuary tax on sugar and soft drinks has also been suggested. Some jurisdictions have also levied taxes on illegal drugs such as cocaine and marijuana.

The revenue generated by sin taxes is sometimes used for special projects, but might also be used in the ordinary budget. American cities and countries have used them to pay for stadiums, while in Sweden the tax for gambling is used for helping people with gambling problems. Acceptance of sumptuary taxes may be greater than income tax or sales tax.

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Metabolism Boosted By Enzyme, Weight Gain Prevented In Mice

Male and female mice engineered to express the inflammatory enzyme IKKbeta in their fat tissue ate more but gained less weight. They burned sugar and fat more effectively than mice who were left unaltered. The research may shed light on how obesity and inflammation affect insulin resistance and sensitivity.
In a new study, scientists report that they substantially curbed weight gain, improved metabolism, and improved the efficacy of insulin in mice by engineering them to express a specific human enzyme in their fat tissue. Although the obesity prevention came at the significant cost of widespread inflammation, the research offers new clues about the connections among obesity, insulin resistance and type 2 diabetes, and inflammation.
"Turning on this molecule has a very dramatic impact on lipid metabolism," said Haiyan Xu, assistant professor of medicine (research) in the Warren Alpert Medical School of Brown University and a researcher at Rhode Island Hospital's Hallett Center for Diabetes and Endocrinology. Xu is the corresponding author of a paper describing the research in the January 2012 issue of Endocrinology and released early online.
The relationship between fat, inflammation, and insulin performance is complex. The conventional wisdom is that obesity leads to inflammation which contributes to insulin resistance. In this study, the researchers changed the sequence of events for transgenically engineered mice by inducing inflammation via the enzyme IKKbeta in their fatty tissue before they were obese. The result for metabolism was much more positive than for control mice who were left unaltered but were fed the same diets.
For both male and female mice, the ones who were altered still put on weight but significantly more slowly. All the mice started at the same weight. After about 22 weeks on a high-fat diet, however, altered male mice weighed less than 38 grams while unaltered male mice weighed more than 45 grams. On a less extravagant diet named "chow" the difference was considerably lessened but was still statistically significant. Both trends held for females as well.
The altered mice experienced slower weight gain despite eating much more food. Their increased metabolism allowed them to dispatch the extra calories much more efficiently. After being injected with glucose, for example, altered mice maintained lower blood sugar levels than unaltered mice. The same was true after insulin injections, suggesting that insulin was more effective. In addition, the transgenic mice expended much more energy than their normal counterparts, suggesting that the sugar was indeed metabolized.
The mechanisms by which IKKbeta in fatty tissue increases metabolic performance are not completely clear, but the researchers measured increased expression of genes associated both with fatty acid oxidation and with making mitochondria, a cell part responsible for producing energy.
One possible lesson from the research seems to be that while obesity and inflammation are both promoters of insulin resistance, Xu said, obesity seems to be the worse one.
"Lower body weight is always a beneficial thing for influencing insulin sensitivity," she said. "Reduced adiposity wins over increased inflammation."
Another point is that IKKbeta's ability to aid metabolism may be specific to its activation in fat tissue. In previous studies, scientists had activated it in the liver with no weight-reduction benefits and in the brain's hypothalamus, leading to increased weight gain.

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