Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pyruvate oxidation is critical determinant of pancreatic islet number and β-cell mass

06.08.2014

Researchers at the University at Buffalo, led by Dr. Mulchand Patel and also at Lawson Health Research Institute and Western Ontario, London, Canada, led by Dr. David Hill, collaboratively evaluated the role of the mitochondrial multienzyme pyruvate dehydrogenase complex in the regulation of pancreatic β-cell development and maturation in the immediate postnatal period in mice.

This study, reported in the August 2014 issue of Experimental Biology and Medicine, demonstrated that the pyruvate dehydrogenase complex is not only required for insulin gene expression and glucose-stimulated insulin secretion, but also directly influences β-cell growth and maturity. This places glucose metabolism as a direct regulator of β-cell mass and plasticity.

Glucose metabolism within the pancreatic β-cells is crucial for insulin gene expression and hormone exocytosis, but there is increasing evidence that glucose metabolic pathways are also important for β-cell development and the maintenance of β-cell mass in adult life.

A targeted deletion of glucokinase in mouse β-cells not only prevents glucose-stimulated insulin secretion, but also β-cell proliferation and is associated with increased apoptosis. A direct manipulation of glucose availability to the embryonic pancreas in tissue culture showed that it was necessary for both α- and β-cell development through the regulation of the transcription factors Neurogenin 3 (Neurog3) and NeuroD.

In the article by Patel et al., the authors show that a targeted β-cell deletion of the α subunit of the pyruvate dehydrogenase component, a major rate-limiting enzyme for the pyruvate dehydrogenase complex that regulates pyruvate metabolism from glucose in the mitochondria, in mouse resulted in reduced insulin availability and glucose-sensitive release as would be expected.

But they also demonstrate that β-cell number was reduced postnatally as was the expression of Neurog3, NeuroD and Pdx1. Interestingly, there was also a reduction in the numbers of insulin-immunopositive, extra-islet small endocrine cell clusters, a possible source of new β-cells from progenitors.

The new findings reinforce the concept that pathways controlling glucose metabolism in β-cells are as important for maintenance of β-cell mass as are hormones and growth factors, such as glucagon-like polypeptide 1 (GLP1).

"These findings show that glucose metabolism is a major regulator of β-cell mass which is likely to act independently of other signaling pathways, such as insulin receptor substrate 2", said Dr. Mulchand Patel, senior author of the study and SUNY Distinguished Professor, Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, the State University of New York.

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "the study by Patel et al utilizes a mouse knockout model to disrupt the pyruvate dehydrogenase complex (PDC) activity to study the role of PDC in pancreatic β-cell development. They demonstrate that PDC has a direct impact upon the regulation of β-cell mass as well as plasticity."

###

Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.sebm.org. If you are interested in publishing in the journal please visit http://ebm.sagepub.com/.

M.S. Patel | Eurek Alert!

Further reports about: Biology Medicine SUNY dehydrogenase islet metabolism pancreatic pathways plasticity

More articles from Life Sciences:

nachricht Opening the cavity floodgates
23.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Incentive to Move
23.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Optical Nanoscope Allows Imaging of Quantum Dots

Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.

Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Researchers reveal how microbes cope in phosphorus-deficient tropical soil

23.01.2018 | Earth Sciences

Opening the cavity floodgates

23.01.2018 | Life Sciences

Siberian scientists suggested a new method for synthesizing a promising magnetic material

23.01.2018 | Materials Sciences

VideoLinks Science & Research
Overview of more VideoLinks >>>