====================================

TREHALOSE - 2004 -

From Recent Publications available on the (Inter-) Net

Simple sugar eases Huntington's disease in mice

Discovery provides taste of a possible route for human drug development.
19 January 2004

http://www.nature.com/nsu/040112/040112-16.html

A simple sugar called trehalose helps to relieve the symptoms of Huntington's disease in mice. The discovery may help researchers to design drug treatments for the human condition.

Huntington's disease is an inherited illness that causes profound cognitive and movement problems. It affects 1 in 10,000 people. There is currently no cure.

Nobuyuki Nukina and colleagues from the RIKEN Brain Science Institute in Saitama, Japan, tested a variety of compounds on a test-tube model of the disease. They discovered that sugar compounds seemed to have a positive effect. They then tested one specific sugar called trehalose on genetically modified mice with Huntington's disease-like symptoms.

Left untreated, the mice develop aggregates of a badly folded brain protein, called Huntingtin. The animals become uncoordinated, lose weight and die young - at about 3 months old.

But when the animals were allowed to drink a weak solution of trehalose for most of their lives, symptoms improved. Sugar-treated rodents had 40% fewer protein aggregates, lived 10% longer and lost 25% less weight. They were also more co-ordinated - they walked more normally and were less likely to fall off a rotating rod.

Trehalose is a naturally occurring sugar that is used in the food industry to sweeten chewing gum and enhance the flavour of some fruit and dairy products. It also boosts shelf life, and is commonly used as a preservative for cultured cells in the laboratory. But the doses consumed by people are likely to differ from those in the study.

Sweet solution?

The sugar is already known to be safe, so the next step is to test it on human patients, says Nukina. But he cautions that clinical trials are needed to assess it before anyone attempts self-treatment.

Although rodent and human conditions share a similar genetic trigger, the protein clumps that occur in mouse brains rarely occur in human patients. So it's not clear how or if the sugar will affect the degenerating human brain. "The work is encouraging, but needs to be reproduced in other, better models of Huntington's disease," says Huntington's disease researcher Ray Truant from McMaster University in Hamilton, Canada.

Nukina thinks that the sugar works by getting into nerve cells, where it prevents the Huntingtin protein from forming aggregates. But there's no evidence that trehalose even makes it to the brain, counters trehalose researcher Fred Levine from the University of California, San Diego. The next step would be to prove this.

The sugar may be working in other ways. Some think that Huntington's disease occurs when the cellular powerhouses known as mitochondria pack up. Trehalose might act as an energy source for human cells, speculates Truant. Drugs that boost cellular energy are already known to be effective in mouse models of Huntington's disease, so trehalose may work in the same way.

References

1. Tanaka, M. et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nature Medicine, published online, doi:10.1038/nm985 (2004). |

Récentes publications disponibles sur le Net, notamment dans le :
	Le Quotidien du Médecin
Article du 20-Jan-2004 par Véronique NGUYEN

LE TREHALOSE inhibe la formation d'agrégats

Un sucre contre la maladie de Huntington

Un sucre pourrait devenir une nouvelle stratégie contre la maladie de Huntington : divers saccharides, notamment le trehalose, peuvent inhiber la formation des agrégats de polyglutamines. Chez la souris, l'administration orale de trehalose améliore les symptômes moteurs et la durée de vie, sans toxicité.

De notre correspondante
à New York

« L'INTERACTION saccharide-polyglutamine, identifiée dans cette étude, débouche donc sur une nouvelle stratégie thérapeutique pour les maladies à polyglutamines », propose l'équipe dirigée par le Dr Nobuyuki Nukina (institut de science cérébrale Riken, Saitama, Japon).
On sait que la maladie de Huntington, maladie neurodégénérative progressive à transmission héréditaire dominante, est causée par une répétition CAG anormale dans le gène de l'huntingtine, une protéine de fonction encore inconnue. Il en résulte une huntingtine anormale, caractérisée par une répétition de glutamine (polyglutamine) qui provoque l'agrégation de la protéine. Ces agrégats insolubles semblent contribuer à la dégénérescence de neurones (et de leurs dendrites) dans le striatum.

Myoglobine mutante de baleine.

Tanaka, Nukina et coll. ont réussi à développer récemment de grandes quantités de myoglobines mutantes de baleine qui contiennent des polyglutamines et peuvent offrir un modèle moléculaire pour les maladies à polyglutamine.
En utilisant cette myoglobine mutante, les chercheurs ont dépisté plus de 200 petites molécules afin d'identifier celles qui pourraient inhiber l'agrégation de la protéine contenant la polyglutamine.
De cette prospection, il ressort que de nombreux saccharides, et notamment le trehalose, sont capables de diminuer in vitro l'agrégation induite par la polyglutamine.

Moins de mouvements anormaux.

Les chercheurs ont testé l'effet du trehalose chez une souris transgénique servant de modèle pour la maladie de Huntington.
Ce sucre a été ajouté à l'eau de boisson (2 %) des souris transgéniques dès un mois après leur naissance. L'observation, à l'âge de 2 mois et 3 mois, montre un net effet protecteur du trehalose : réduction des agrégats dans le cerveau et moins de mouvements anormaux.

De plus, leur durée de vie est allongée.
Ces effets bénéfiques, suggèrent les chercheurs, résultent de la liaison du trehalose aux polyglutamines, qui stabilise la protéine partiellement dépliée. Le sucre prévient donc la formation de nouveaux agrégats, mais ne peut pas les dissoudre une fois qu'ils sont formés.
Etant donné son absence de toxicité et son efficacité par voie orale, « le trehalose représente un agent thérapeutique ou un chef de file prometteur pour le traitement des maladies à polyglutamine », pensent les chercheurs.
Le trehalose n'a pas affecté la glycémie à jeun des souris, ont-ils constaté, encore que cela devra être soigneusement évalué chez les patients porteurs de la maladie de Huntington.

> Dr VERONIQUE NGUYEN

Nature Medicine », 18 janvier 2004, DOI : 10.1038/nm985

NDLS- Amcan : 1°) Glycémie

NDLS- Amcan : 2°) Amcan Ingrédients est à la disposition des Professionnels de la Santé, des Milieux Associatifs concernés- et sous leur contrôle - pour mettre à leur disposition gracieusement une grande quantité d'échantillons de Tréhalose dont les données spécifiques et techniques du produit sont fournies sur notre Site-Web .

Pour demander vos échantillons, SVP Email

Energy benefits

Trehalose - an ideal energy provider for an active lifestyle

Introduction

Trehalose is a 'new' naturally occurring non-reducing disaccharide composed of two glucose molecules linked by an a 1-1 bond. This linkage in sugars is rare and confers high stability to the molecule, and also provides unique functional and nutritional properties. Trehalose occurs widely in nature and has been consumed regularly in small quantities as part of our diet. Commercially, trehalose is produced from starch by a proprietary enzymatic process developed by the Hayashibara Company, Okayama, Japan. It is now available in Europe as a new food ingredient and has full regulatory approval.¹

Trehalose is a non-reducing sugar that is highly process and shelf stable. It is only half the sweetness of sucrose, but is similar in its functionality, and can be readily used in a wide range of food products including beverages, chocolate and sugar confectionery, bakery products, ice cream and dairy products.

It is a fully caloric sugar. Once ingested trehalose is broken down to glucose by the specific enzyme trehalase, found in the small intestine². However, it has a lower insulin response and a prolonged glucose release when compared with many other sugars, such as glucose and maltose³. These properties combined with its low cariogenicity⁴ and low sweetness makes trehalose an ideal energy source in food and beverage products specifically formulated for the 'lifestyle' and 'sports' nutrition markets.

Product Opportunities

Lifestyle products Trehalose is an ideal carbohydrate for use in lifestyle products, which are formulated to alleviate fatigue and stress in a busy lifestyle. The properties of trehalose, which make it particularly suited for use in this area are:
- Its pattern of energy release results in lower peaks and shallower troughs in blood glucose

- Longer period of energy availability

- Lower insulin response

- Better mental alertness
Sports nutrition products Trehalose has been shown to be a suitable energy source when consumed before, during and after exercise. The properties of trehalose, which make it particularly suited for these products are:
- Does not promote excessive insulin release

- Lower peak glucose and more sustained energy release

- Empties quickly from the stomach

- Low caries-promoting properties

- Palatable, but not too sweet

- Non laxative

Key Scientific Findings

A research programme to evaluate the biochemical and nutritional properties of trehalose has been carried out. The key findings were:

1. Lower blood glucose

'In glucose tolerance trials there is a lower blood glucose peak, and a more sustained release of energy compared with glucose'

The pattern of glucose release is different for trehalose compared to glucose or maltose. In a number of studies, carried out with various concentration of trehalose ranging from 5-20% sugar, lower peak blood glucose is seen when compared to glucose^5,6,7 and maltose⁶ in glucose tolerance tests. For details see Figures 1 below.

In addition, the release of glucose has been shown to be sustained for a longer period when compared to either glucose^5,6 or maltose⁶. See Figure 1.

The benefit of this more sustained release of energy may be in either physical performance or mental alertness.

wpe1.jpg (27690 bytes)

2. Lower blood insulin response

'Trehalose produces a significantly lower insulin response compared to glucose'

A delayed and significantly lower peak insulin profile has been shown in all studies when compared to glucose or maltose^3,5,6,7. For details see Figure 2 below. This profile of insulin release is associated with foods of lower glycaemic index, which is particularly suitable in pre-exercise foods and beverages and for diabetics.

wpe2.jpg (26915 bytes)

3. Prolonged energy availability

'Trehalose is an ideal energy source, prior to, during and after exercise'

Trehalose is a suitable sugar to be taken during exercise and results in significant performance enhancement compared to placebo⁸. A similar level of performance is seen when compared to glucose^7,5, but without the insulin surge associated with glucose. In fact, when trehalose was given, the insulin response throughout the exercise study was lower than with glucose⁷. This is beneficial, as there is less interference with fat mobilisation, which provides an alternative source of energy.

Trehalose empties more quickly from the stomach than either glucose or maltose, in the first 60 minutes after consumption⁶, indicating it is rapidly available to the body.

Trehalose is well tolerated, even at high levels of intake (96g)⁷ there have been no reports of intestinal disturbance.

4. Lower cariogenicity

'Trehalose has a lower caries potential compared to glucose and sucrose'

The effect of trehalose on plaque pH was determined in a study carried out at the University of Leeds⁴. The study compared the acidogenicity of a 10% solution of trehalose compared to sucrose and sorbitol in ten volunteers. For trehalose the minimum plaque pH was significantly higher than sucrose, and the maximum drop in plaque pH and area under the curve, significantly lower. These factors are consistent with trehalose having a lower potential for producing acid, and importantly the pH never dropped to 5.7 - the critical pH for enamel demineralisation. The resulting pH curve for trehalose was more similar to sorbitol than sucrose.

Confectionery products manufactured from trehalose have been evaluated in two studies using plaque pH telemetry^9,10. In both studies plaque pH failed to fall below 5.7 within 30 minutes, indicating the low cariogenicity of these trehalose confectionery products.

5. Better mental alertness

A wide range of factors including "hunger", "fullness", and "sleepiness" was assessed using visual analogue reports during the sugar tolerance studies carried out by French⁶. Compared to glucose or maltose only the trehalose scores for sleepiness were lower. These preliminary findings indicate the practical value of the pattern of energy release from trehalose.

References

^1-Trehalose: acceptance for use as Novel Food, Commission Decision of 25 September 2001.
²-Murray IA, Coupland K, Smith JA, Ansell D and Long RA. (2000) Intestinal trehalase in a UK population; establishing a normal range and the effect of disease. Brit J Nutr; 83: 241-5.
³-Oku T,and Nakamura S (2000) Estimation of intestinal trehalase activity from a laxative threshold of trehalose and lactulose on healthy female subjects. Eur J Clin Nutr; 54: 783-8.
⁴-Pollard MA and Curzen ME J (1996). Report to British Sugar. The effect of trehalose on plaque pH, University of Leeds, UK.
5-Gleeson M and Bishop NC (2000). Report to British Sugar. Studies on the potential use of trehalose as an ingredient of sports beverage; Study 1 the Glycaemic index of trehalose, University of Birmingham, UK.
⁶-French S, Bradley S, Arnold M, Moses W A, Harland J I, Cooper J, Botham L and Langhans W (2001). Effects of trehalose on blood glucose, insulin, incretin hormones and gastric emptying in healthy human volunteers, submitted for publication.
^7-Ivy J L (2001) Report to Cargill. The glycaemic index and performance enhancing capacity of trehalose, University of Texas, USA.
8-Gleeson M and Bishop NC (2000). Report to British Sugar. Studies on the potential use of trehalose as an ingredient of sports beverage; Study 2 effects of trehalose, glucose, or placebo ingestion on metabolic responses, perception of effort and endurance performance during constant load cycling to fatigue, University of Birmingham, UK.
^9-Zappa U (1997) Report to British Sugar. pH telemetry expert opinion referring to safe for teeth properties ref. 85 trehalose, University of Basel, Switzerland.
^10-Personal communication Kazuhikio et al, University of Tohoku (1997) Assessment of the acid production following consumption of chocolate containing trehalose in human dental plaque by the oral electrode method.

Dr Janice Harland, R Nutr.
Nutrition Consultant
January 2002

Diabetes
March 1997 Volume 46, Number 3

Trehalose: A Cryoprotectant That Enhances Recovery and Preserves Function of Human Pancreatic Islets After Long-Term Storage

Gillian M. Beattie, John H. Crowe, Ana D. Lopez, Vincenzo Cirulli, Camillo Ricordi, and Alberto Hayek

The scarcity of available tissue for transplantation in diabetes and the need for multiple donors make it mandatory to use an optimal cryopreservation method that allows maximal recovery and preservation of ß-cell function. We have developed a method to cryopreserve islets with excellent survival of endocrine cells. Current methods use DMSO as cryoprotectant. Our method involves introducing both DMSO and the disaccharide trehalose into the cells during cooling. Uptake and release of trehalose occurred during the thermotropic lipid-phase transition measured in pancreatic endocrine cells between 5° and 9°C, using [¹⁴C]trehalose. Recovery of adult islets after cryopreservation with 300 mmol/l trehalose was 92 vs. 58% using DMSO alone. In vitro function, in terms of insulin content and release in response to secretagogues, was indistinguishable from fresh islets. Grafts from islets cryopreserved with trehalose contained 14-fold more insulin than grafts from islets cryopreserved without trehalose. Results with human fetal islet-like cell clusters (ICCs) were more pronounced: recovery from cryopreservation was 94%, compared with 42% without trehalose. Complete functionality of fetal cells was also restored; tritiated thymidine incorporation and insulin content and release were similar to fresh tissue. After transplantation in nude mice, there was a 15-fold increase in insulin content of grafts from ICCs cryopreserved with trehalose compared with ICCs cryopreserved without trehalose. Thus, the addition of trehalose to cryopreservation protocols leads to previously unobtainable survival rates of human pancreatic endocrine tissue.

Diabetes 46:X523, 1997

.......page suivante / continue......