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 Scientists coax proteins to form synthetic structures with method that mimics nature
15.01.2019 | University of Texas at Austin

nachricht DNA library of apoid wasps published
15.01.2019 | Staatliche Naturwissenschaftliche Sammlungen Bayerns

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

Im Focus: Elucidating the Atomic Mechanism of Superlubricity

The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.

One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...

Im Focus: Mission completed – EU partners successfully test new technologies for space robots in Morocco

Just in time for Christmas, a Mars-analogue mission in Morocco, coordinated by the Robotics Innovation Center of the German Research Center for Artificial Intelligence (DFKI) as part of the SRC project FACILITATORS, has been successfully completed. SRC, the Strategic Research Cluster on Space Robotics Technologies, is a program of the European Union to support research and development in space technologies. From mid-November to mid-December 2018, a team of more than 30 scientists from 11 countries tested technologies for future exploration of Mars and Moon in the desert of the Maghreb state.

Close to the border with Algeria, the Erfoud region in Morocco – known to tourists for its impressive sand dunes – offered ideal conditions for the four-week...

Im Focus: Programming light on a chip

Research opens doors in photonic quantum information processing, optical signal processing and microwave photonics

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a new integrated photonics platform that can...

Im Focus: Physicists uncover new competing state of matter in superconducting material

A team of experimentalists at the U.S. Department of Energy's Ames Laboratory and theoreticians at University of Alabama Birmingham discovered a remarkably long-lived new state of matter in an iron pnictide superconductor, which reveals a laser-induced formation of collective behaviors that compete with superconductivity.

"Superconductivity is a strange state of matter, in which the pairing of electrons makes them move faster," said Jigang Wang, Ames Laboratory physicist and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

 
Latest News

Scientists coax proteins to form synthetic structures with method that mimics nature

15.01.2019 | Life Sciences

Next generation photonic memory devices are light-written, ultrafast and energy efficient

15.01.2019 | Information Technology

Viennese scientists develop promising new type of polymers

15.01.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>