Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists use transcription factors to increase insulin production in diabetic mice

14.04.2005


A group of Japanese scientists has used gene therapy to deliver three insulin transcription factors, MafA, PDX-1, and NeuroD, to the livers of diabetic mice. As a result, the mice experienced an increase in insulin gene expression and insulin production, raising the possibility that this could eventually be used to treat diabetes. The research appears as the "Paper of the Week" in the April 15 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Diabetes, which is marked by high blood-sugar levels, results when the body is unable to produce a sufficient amount of insulin or when it is unable to use insulin properly. There are several ways to restore normal blood sugar levels, including administration of insulin or pancreas and islet transplantation. However, the former involves daily injections and the latter requires life-long immunosuppressive therapy and is limited by tissue supply.

An alternative way to increase the amount of insulin circulating in the body is to enhance insulin gene transcription which in turn results in an increase in the production of insulin. One possible way to do this is by increasing the body’s production of transcription factors, the molecules that are in charge of turning gene transcription on and off.



Dr. Hideaki Kaneto, of the Osaka University Graduate School of Medicine, and his colleagues did just that and over-expressed the insulin transcription factors MafA, PDX-1, and NeuroD in the liver of mice. The researchers did this by inserting the transcription factors into adenovirus and then injecting the adenovirus into the cervical vein of the mice. Each transcription factor was detected only in the liver and not in other tissues after infection with the adenovirus. The result was that the mice had a marked increase in insulin gene expression and therefore insulin production.

The researchers also discovered that overexpression of these three transcription factors in the livers of diabetic mice dramatically ameliorated glucose tolerance in these animals. "Glucose tolerance is a capacity to maintain normal glucose levels in our body," explains Dr. Kaneto. "Under normal conditions, insulin is released from pancreatic beta-cells after glucose load. The released insulin facilitates glucose uptake into peripheral tissues such as muscle and fat and suppresses glucose production in the liver in order to maintain glucose tolerance. In contrast, under diabetic conditions, beta-cell dysfunction and insulin resistance are often observed, which disturbs glucose tolerance."

PDX-1 and NeuroD are transcription factors that are found in the pancreas. They play a crucial role in pancreas development and beta-cell differentiation and also maintain normal beta-cell function by regulating several beta-cell-related genes including insulin. While these two transcription factors contributed to the increase in insulin gene expression, MafA was the most important molecule in this study. The researchers discovered that a combination of only PDX-1 and NeuroD was much less effective at increasing insulin production than all three transcription factors together.

"MafA, a recently isolated transcription factor, is expressed only in pancreatic beta-cells and is very important for insulin gene expression," notes Dr. Kaneto. "In this study, we show that MafA overexpression, together with some other pancreatic factors, markedly increases insulin gene expression in the liver, and dramatically decreases blood glucose levels in diabetic mice. These results suggest a crucial role of MafA as a novel therapeutic target for diabetes."

Although this technique is successful in mice, adenovirus cannot be used to deliver genes into humans. Thus, it will be necessary to modify the vector or to develop some other technique to deliver the transcription factor genes into humans.

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org
http://www.jbc.org

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>