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!
New method opens crystal clear views of biomolecules
11.02.2016 | Deutsches Elektronen-Synchrotron DESY
Scientists from MIPT gain insights into 'forbidden' chemistry
11.02.2016 | Moscow Institute of Physics and Technology
Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include yeast and crop plants, such as maize and potato – plants with high demands. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.
The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug...
Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".
Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...
The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.
Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...
Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.
The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).
Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels
A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...
09.02.2016 | Event News
02.02.2016 | Event News
26.01.2016 | Event News
11.02.2016 | Life Sciences
11.02.2016 | Physics and Astronomy
11.02.2016 | Earth Sciences