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 Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>