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 How to become a T follicular helper cell
31.07.2015 | La Jolla Institute for Allergy and Immunology

nachricht Heating and cooling with light leads to ultrafast DNA diagnostics
31.07.2015 | University of California - Berkeley

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum Matter Stuck in Unrest

Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.

What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...

Im Focus: On the crest of the wave: Electronics on a time scale shorter than a cycle of light

Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.

The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

Im Focus: Unlocking the rice immune system

Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight

A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...

Im Focus: Smarter window materials can control light and energy

Researchers in the Cockrell School of Engineering at The University of Texas at Austin are one step closer to delivering smart windows with a new level of energy efficiency, engineering materials that allow windows to reveal light without transferring heat and, conversely, to block light while allowing heat transmission, as described in two new research papers.

By allowing indoor occupants to more precisely control the energy and sunlight passing through a window, the new materials could significantly reduce costs for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

 
Latest News

Tool making and additive technology exhibition: Fraunhofer IPT at Formnext

31.07.2015 | Trade Fair News

First Siemens-built Thameslink train arrives in London

31.07.2015 | Transportation and Logistics

California 'rain debt' equal to average full year of precipitation

31.07.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>