Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutation in tumor suppressor gene causes pancreatic islet cells to reproduce

06.07.2006
Cancer biology discovery could lead to new diabetes treatment

Researchers at the University of Pennsylvania School of Medicine have found that the acute loss of a protein called menin can cause the proliferation of pancreatic islet cells, which secrete insulin to regulate blood sugar. The menin gene (Men1) mutation in humans causes an inherited disease called Multiple Endocrine Neoplasia type 1 (MEN1). Not only could this discovery inform basic cancer biology, it also has implications for treating Type 1 diabetes. The researchers report their findings in the latest issue of Cancer Research.


Comparison of islet cell proliferation in pancreatic islets with (left panel) and without (right panel) menin protein. The pink dots within the dashed yellow circle -- indicated by the red arrows -- represent proliferating islet cells. More proliferating cells (pink dots) appear in islets without menin (right). Credit: Ya-Xiong Chen, Ph.D., University of Pennsylvania School of Medicine, and Cancer Research, June 2006

MEN1 patients develop mostly benign tumors or hyperplasia (over proliferation of cells) in several endocrine organs, such as parathyroids and pancreatic islet cells. Normally, the menin protein has a tumor-suppressing or cell-proliferation-suppressing function. Loss of menin can cause proliferation of pancreatic islet cells, but not the adjacent exocrine cells that secrete proteins other than insulin.

The researchers developed an animal model that allowed for precise timing in "cutting" the Men1 gene from the genome of knock-out mice. They showed that within seven days of excising Men1, pancreatic islet cells proliferated in the mice. Previously, other labs could only see proliferating islet cells after months of Men1 excision because they could not precisely time the process. "Our results show an acute effect of Men1 excision and directly link Men1 to repression of pancreatic islet cell proliferation," says senior author Xianxin Hua, MD, PhD, Assistant Professor of Cancer Biology at Penn's Abramson Family Cancer Research Institute.

The researchers excised Men1, the gene encoding the protein menin, from both islet cells and adjacent exocrine cells in the pancreas, but only in islet cells did they observe cells proliferating. This is important because Men1 mutations largely cause endocrine hyperplasia or tumors, but not exocrine tumors. "Our results showing preferential effects on islet-cell proliferation could at least in part explain that the loss of menin only leads to endocrine tumors," explains Hua.

In type I diabetes, the loss of islet beta cells is the leading reason why a sufficient amount of insulin cannot be produced. "If we could eventually repress menin function to specifically stimulate beta-cell proliferation, this may facilitate devising new strategies to increase insulin-secreting beta cells and treating diabetes," notes Hua.

"We did not expect the connection between a study about a tumor suppressor and a potential new avenue for treating diabetes," he adds. "By taking advantage of studying a genetically well-characterized tumor syndrome, MEN1, we set out to understand how the first step of benign tumor development is precisely controlled. The more we discovered about menin function, the better we understood the precise role of menin in regulating islet cell proliferation. This latest finding about the acute and specific role of menin on repressing islet cells, but not adjacent exocrine cells, led to the realization that manipulating the menin pathway might be a powerful way to stimulate islet cell proliferation to fight type I diabetes, although we are just beginning toward that goal."

Study co-authors are Robert B. Schnepp, Ya-Xiong, Haoren Wang, Tim Cash, Albert Silva, Alan Diehl, and Eric Brown, with participation from the members of Dr. Eric Brown's lab and Dr. Alan Diehl's lab, all from Penn. This research was funded by the National Institutes of Health.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu/

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>