Featured Research

from universities, journals, and other organizations

Pyruvate oxidation is critical determinant of pancreatic islet number, beta-cell mass

Date:
August 5, 2014
Source:
Society for Experimental Biology and Medicine
Summary:
Glucose is not only a major nutrient regulator of insulin secretion, but also impacts on gene expression in beta-cells. Using a mouse model of beta-cell-specific knock-out of Pdha1 gene which encodes the alpha subunit of the pyruvate dehydrogenase component of the pyruvate dehydrogenase complex, the authors demonstrated that mitochondrial metabolism of pyruvate derived from glucose not only regulates insulin secretion but also directly influences beta-cell growth and plasticity.

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.

Related Articles


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."


Story Source:

The above story is based on materials provided by Society for Experimental Biology and Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. S. Patel, M. Srinivasan, B. Strutt, S. Mahmood, D. J. Hill. Featured Article: Beta cell specific pyruvate dehydrogenase alpha gene deletion results in a reduced islet number and beta-cell mass postnatally. Experimental Biology and Medicine, 2014; 239 (8): 975 DOI: 10.1177/1535370214531895

Cite This Page:

Society for Experimental Biology and Medicine. "Pyruvate oxidation is critical determinant of pancreatic islet number, beta-cell mass." ScienceDaily. ScienceDaily, 5 August 2014. <www.sciencedaily.com/releases/2014/08/140805150851.htm>.
Society for Experimental Biology and Medicine. (2014, August 5). Pyruvate oxidation is critical determinant of pancreatic islet number, beta-cell mass. ScienceDaily. Retrieved November 1, 2014 from www.sciencedaily.com/releases/2014/08/140805150851.htm
Society for Experimental Biology and Medicine. "Pyruvate oxidation is critical determinant of pancreatic islet number, beta-cell mass." ScienceDaily. www.sciencedaily.com/releases/2014/08/140805150851.htm (accessed November 1, 2014).

Share This



More Health & Medicine News

Saturday, November 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Melafind: Spotting Melanoma Without a Biopsy

Melafind: Spotting Melanoma Without a Biopsy

Ivanhoe (Oct. 31, 2014) The MelaFind device is a pain-free way to check suspicious moles for melanoma, without the need for a biopsy. Video provided by Ivanhoe
Powered by NewsLook.com
Battling Multiple Myeloma

Battling Multiple Myeloma

Ivanhoe (Oct. 31, 2014) The answer isn’t always found in new drugs – repurposing an ‘old’ drug that could mean better multiple myeloma treatment, and hope. Video provided by Ivanhoe
Powered by NewsLook.com
Chronic Inflammation and Prostate Cancer

Chronic Inflammation and Prostate Cancer

Ivanhoe (Oct. 31, 2014) New information that is linking chronic inflammation in the prostate and prostate cancer, which may help doctors and patients prevent cancer in the future. Video provided by Ivanhoe
Powered by NewsLook.com
Sickle Cell: Stopping Kids’ Silent Strokes

Sickle Cell: Stopping Kids’ Silent Strokes

Ivanhoe (Oct. 31, 2014) Blood transfusions are proving crucial to young sickle cell patients by helping prevent strokes, even when there is no outward sign of brain injury. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins