Navigation Links
Pyruvate oxidation is critical determinant of pancreatic islet number and β-cell mass
Date:8/5/2014

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."


'/>"/>

Contact: M.S. Patel
mspatel@buffalo.edu
Society for Experimental Biology and Medicine
Source:Eurekalert

Related medicine news :

1. UV Technologies, LLC, Makers of UV-Aid® Release Results of Study Showing Photo-Oxidation Technology Highly Effective in Preventing Colds, Flu, and Ear Infections
2. Pitt: Targeted oxidation-blocker prevents secondary damage after traumatic brain injury
3. The Critical Bench Program 2.0 Pdf Review Exposes Mike Westerdal's Guide for Increasing Bench Press – Vkool.com
4. Women’s Health Organization Critical of Always “Like a Girl” Ad
5. Critical Care Therapeutics in Major Developed Market is Expected to Grow at a CAGR of 4.7% to $2.5 Billion in 2019
6. Researchers find gene critical for development of brain motor center
7. Nurses play critical role in responding to global resurgence of pertussis
8. $2.3 million NIH grant to UCF will help improve critical patient care
9. Scientists generate long-sought molecular map of critical genetic machinery
10. Overestimation of radiation exposure may keep women from critical screening
11. Food shortages could be most critical world issue by mid-century
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... Montreal, Canada (PRWEB) , ... June 25, 2016 , ... ... the pursuit of success. In terms of the latter, setting the bar too high ... low, risk more than just slow progress toward their goal. , Research from ...
(Date:6/24/2016)... ... June 24, 2016 , ... Marcy was in a crisis. Her son James, eight, was ... his family verbally and physically. , “When something upset him, he couldn’t control his emotions,” ... He would throw rocks at my other children and say he was going to kill ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, ... and the Road To Recovery® program to drive cancer patients to and from their ... to ensure the highest quality of life and ongoing independence. Getting to and ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Haute Beauty Network, affiliated ... Weintraub as a prominent plastic surgeon and the network’s newest partner. , ... most handsome men, look naturally attractive. Plastic surgery should be invisible.” He stands ...
(Date:6/24/2016)... ... ... Venture Construction Group (VCG) sponsors Luke’s Wings 5th Annual ... Country Club at 1201 Rockville Pike, Rockville, Maryland, 20852. The event raised funds ... been wounded in battle and their families. Venture Construction Group is a 2016 Silver ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016   Pulmatrix, Inc ., (NASDAQ: ... innovative inhaled drugs, announced today that it was added ... reconstituted its comprehensive set of U.S. and global ... is an important milestone for Pulmatrix," said Chief Executive ... awareness of our progress in developing drugs for crucial ...
(Date:6/23/2016)... , June 23, 2016 Any dentist who ... challenges of the current process. Many of them do not ... the technical difficulties and high laboratory costs involved. And those ... offer it at such a high cost that the majority ... Dr. Parsa Zadeh , founder of Dental ...
(Date:6/23/2016)... , June 23, 2016 ... CAPR ), a biotechnology company focused on the ... announced that patient enrollment in its ongoing randomized ... has exceeded 50% of its 24-patient target. Capricor ... the third quarter of 2016, and to report ...
Breaking Medicine Technology: