Red Wine Chemical May Treat Diabetes

Resveratrol Lowers Blood Sugar Levels, Improves Insulin Levels in Mouse Study

(WebMD)  The much touted compound resveratrol shows some promise as a future treatment for type 2 diabetes, but drinking wine or taking resveratrol supplements isn't likely to do diabetic people much good, researchers say.

Resveratrol, found in red wine, was found to lower blood sugar levels and improve insulin levels when injected directly into the brains of mice fed very high-calorie diets in a study conducted by researchers at the University of Texas Southwestern Medical Center (UTSW).

The finding suggests that the brain plays a key role in resveratrol's
beneficial effect on diabetes and that the benefits may occur independently of diet and body weight.

If this is true, new type 2 diabetes treatments targeting the brain may be possible, lead researcher Roberto Coppari, PhD, tells WebMD.

But drinking red wine is not likely to improve blood sugar and insulin
levels because resveratrol does not cross the blood-brain barrier very efficiently.

"We don't want to send the message that you can treat diabetes by drinking red wine," Coppari tells WebMD. "Two or three glasses a day wouldn't be nearly enough for the brain to accumulate the amount of resveratrol delivered in our study. It would take many, many bottles, and clearly that wouldn't be good for you."

Resveratrol: Fountain of Youth?
Resveratrol first made headlines several years ago when researchers identified it as the substance likely responsible for the health benefits to the heart attributed to red wine.

The buzz became almost deafening early this year, when the news program 60 Minutes aired a story suggesting that resveratrol-based drugs may one day succeed in slowing aging in humans.

Found mostly in the skin of red grapes and other dark fruits, resveratrol has been shown to protect against diabetes in studies involving mice, although very high doses of the molecule have been needed.

In the newly published study, Coppari and colleagues examined whether injecting resveratrol directly into the brains of diabetic mice would activate a group of proteins known as sirtuins, which have been shown to have anti-diabetes properties in earlier animal studies.

The UTSW researchers injected one group of diabetic mice with resveratrol, while a second group was given saline-containing placebo injections.

All the mice were fed a very high-fat diet throughout the study.

Despite this, insulin levels in the resveratrol-treated mice dropped
significantly and were halfway to normal by the end of the five-week study. Insulin levels among the placebo-treated mice continued to rise.

Resveratrol Activates SIRT1
The resveratrol injections were found to activate SIRT1 proteins in the brain and they reduced brain inflammation related to the mice's high-calorie diets.

The study was published this week online and it will appear in the December issue of the journal Endocrinology.

"The brain appears to be a major player in diabetes," Coppari says. "The treatments we have for diabetes target other organs like the liver. The brain hasn't really been on the map."

If the findings are confirmed, Coppari believes the brain could become a target for not only diabetes treatments, but treatments for cardiovascular disease and obesity as well.

The study is not the first to show that resveratrol can prevent the deleterious consequences of a high-fat diet. In November of 2006, researchers from Harvard Medical School and the National Institute on Aging reported that obese mice fed a diet containing 60 percent of calories from fat lived significantly longer if they were treated with resveratrol.

The resveratrol-treated mice lived as long as lean mice, with a much better quality of life, as measured by motor skills tests.

"After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice," study co-author Rafael de Cabo, PhD, of the National Institutes of Aging says in a news release.

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Chem Biol Drug Des. 2009 Oct 20. [Epub ahead of print]

Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity.

Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M.

Department of Neuroscience, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD(+)-dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys-SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys-SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53-derived peptide substrate or acetylated PGC-1alpha isolated from cells, and (iii) although SIRT1 deacetylates PGC-1alpha in both in vitro and cell-based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1.

[jamesinraro]

Resveratrol can only be effective if your supplier actually gives you what you purchase and the amount of trans-resveratrol conforms to the product's label claims. Consumer Lab, the recognized independent authority on supplement and over the counter drug testing, evaluated the major brands of resveratrol recently and found many lacking in content and quality. None of the newer companies, most of which use some form of the word resveratrol in their name, agreed to have their products tested. The highest potency products that passed their evaluation were Biotivia?s Transmax and Bioforte. Bioforte was also the lowest price per mg of active ingredient. The test was open to all brands. The results are on the ConsumerLab web site. Also,in tests done by the University of Bologne, Italy it was found that almost 80% of all so-called resveratrol products contained either no trans-resveratrol or less than ten percent of the label claimed amount of this essential compound. This is clearly a case of buyer beware.