Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find promising drug for preventing serious complications of diabetes

17.02.2003


Results reported in Nature Medicine



Opening up the possibility of a new approach to the treatment of diabetes, researchers have shown in animal studies that a drug long available in Europe can simultaneously block three of the major biochemical pathways responsible for the blood-vessel damage that causes serious diabetic complications.

Dr. Michael Brownlee of the Albert Einstein College of Medicine was the senior researcher for the international consortium that carried out the study, which appears in the current issue of Nature Medicine.


Research over the past 30 years has identified four biochemical pathways by which diabetes injures blood vessels - damage that makes diabetes the leading cause of blindness, kidney failure, heart attacks and nontraumatic amputation of legs in the U.S. In this study, from the Einstein Diabetes Research Center, the drug benfotiamine completely blocked three of those pathways when tested in diabetic rats, animals often used as models for studying the disease. Benfotiamine is a synthetic derivative of thiamine (vitamin B1) and has been available for more than a decade in Germany. It is prescribed there for treating diabetic neuropathy, sciatica and other painful nerve conditions but has never been tested in placebo-controlled, double-blind clinical trials.

In people with diabetes, all cells are bathed in blood that contains elevated levels of glucose. Most cells still manage to keep their internal glucose at normal levels. But certain cells - particularly endothelial cells that line arteries and the capillaries of the retina and kidney - are unable to regulate glucose and instead develop high internal levels of the sugar, which they can’t completely metabolize. As a result, glucose-derived "intermediate" metabolic products accumulate inside these cells, where they activate pathways of cellular damage that can eventually lead to blindness and other complications.

Dr. Brownlee and his colleagues focused on two glucose-derived intermediates that activate three of the damaging biochemical pathways. They knew that both of these metabolic compounds (fructose-6-phosphate and glyceraldehyde-3-phosphate) are the end products of another biochemical pathway mediated by an enzyme called transketolase.

By boosting transketolase’s activity, the researchers reasoned, they might be able to reverse this pathway - essentially converting the two damage-triggering glucose metabolites into harmless chemicals and preventing all three damaging biochemical pathways from being activated. They also knew that transketolase, like many enzymes, depends on a cofactor for its activity - in this case thiamine.

In preliminary studies involving arterial endothelial cells, adding standard thiamine boosted transketolase’s activity by only 20 percent, so the researchers looked around for a more potent form of thiamine. Dr. Brownlee’s German colleagues suggested benfotiamine, a fat-soluble thiamine derivative.

"By pure serendipity, it turned out that benfotiamine boosted the activity of the enzyme transketolase by 300 to 400 percent - something we never could have predicted based on benfotiamine’s chemical structure," says Dr. Brownlee, who is professor of medicine and of pathology, and the Anita and Jack Saltz Professor of Diabetes Research at Einstein.

As reported in the Nature Medicine paper, benfotiamine successfully blocked all three major destructive biochemical pathways in experiments with arterial endothelial cells. Next, the researchers treated diabetic rats with benfotiamine and then examined their retinal tissue. (For comparison, they also examined the retinas of control diabetic rats and normal rats.)

Chemical analysis showed that all three biochemical pathways had been "normalized" in the benfotiamine-treated diabetic rats so that their retinas were biochemically identical to the retinas of normal rats. The drug also prevented diabetic retinopathy in the animals, since microscopic examination revealed that the retinas of benfotiamine-treated diabetic rats were free of vascular damage.

No drug for preventing the complications of diabetes is currently available. Dr. Brownlee is applying to the U.S. Food and Drug Administration to test benfotiamine as an Investigational New Drug. Noting that drugs that produce impressive results in animals do not always work in humans, Dr. Brownlee says he is reasonably confident that benfotiamine will at least prove to be safe: "Benfotiamine has been used extensively in Germany for many years, and to my knowledge there are no reported side effects."

Dr. Brownlee cautions people with diabetes against taking thiamine supplements, however, noting that there is no evidence that thiamine can activate transketolase sufficiently to prevent complications of diabetes.


In addition to Dr. Brownlee and his Einstein colleagues, authors of the Nature Medicine paper included scientists from Germany, Italy, China and Japan. The research was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association and the Juvenile Diabetes Research Foundation.




Karen Gardner | EurekAlert!
Further information:
http://www.aecom.yu.edu/

More articles from Health and Medicine:

nachricht Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.

Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

30.09.2016 | Materials Sciences

New Technique for Finding Weakness in Earth’s Crust

30.09.2016 | Earth Sciences

Cells migrate collectively by intermittent bursts of activity

30.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>