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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/11549
Title: Differences between human and rodent pancreatic islets: Low pyruvate carboxylase, ATP citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets
Authors: Michael J. MacDonald
Melissa J. Longacre
Scott W. Stoker
Mindy Kendrick
Ansaya Thonpho
Laura J. Brown
Noaman M. Hasan
Sarawut Jitrapakdee
Toshiyuki Fukao
Matthew S. Hanson
Luis A. Fernandez
Jon Odorico
University of Wisconsin School of Medicine and Public Health
Mahidol University
Gifu University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 27-May-2011
Citation: Journal of Biological Chemistry. Vol.286, No.21 (2011), 18383-18396
Abstract: Anaplerosis, the net synthesis in mitochondria of citric acid cycle intermediates, and cataplerosis, their export to the cytosol, have been shown to be important for insulin secretion in rodent beta cells. However, human islets may be different. We observed that the enzyme activity, protein level, and relative mRNA level of the key anaplerotic enzyme pyruvate carboxylase (PC) were 80-90% lower in human pancreatic islets compared with islets of rats and mice and the rat insulinoma cell line INS-1 832/13. Activity and protein of ATP citrate lyase, which uses anaplerotic products in the cytosol, were 60-75% lower in human islets than in rodent islets or the cell line. In line with the lower PC, the percentage of glucose-derived pyruvate that entered mitochondrial metabolism via carboxylation in human islets was only 20-30% that in rat islets. This suggests human islets depend less on pyruvate carboxylation than rodent models that were used to establish the role of PC in insulin secretion. Human islets possessed high levels of succinyl-CoA:3-ketoacid-CoA transferase, an enzyme that forms acetoacetate in the mitochondria, and acetoacetyl-CoA synthetase, which uses acetoacetate to form acyl-CoAs in the cytosol. Glucose-stimulated human islets released insulin similarly to rat islets but formed much more acetoacetate. β-Hydroxybutyrate augmented insulin secretion in human islets. This information supports previous data that indicate beta cells can use a pathway involving succinyl-CoA:3-ketoacid-CoA transferase and acetoacetyl-CoA synthetase to synthesize and use acetoacetate and suggests human islets may use this pathway more than PC and citrate to form cytosolic acyl-CoAs. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79956322775&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/11549
ISSN: 1083351X
00219258
Appears in Collections:Scopus 2011-2015

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