AJP - Endo Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 288: E471-E478, 2005. First published October 26, 2004; doi:10.1152/ajpendo.00427.2004
0193-1849/05 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/3/E471    most recent
00427.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, Y. Q.
Right arrow Articles by Long, Y. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, Y. Q.
Right arrow Articles by Long, Y. S.

Enhanced rat {beta}-cell proliferation in 60% pancreatectomized islets by increased glucose metabolic flux through pyruvate carboxylase pathway

Y. Q. Liu,1,2 J. Han,1 P. N. Epstein,1,2 and Y. S. Long1

1Kosair Children's Hospital Research Institute, Department of Pediatrics, and 2Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky

Submitted 10 September 2004 ; accepted in final form 24 October 2004

Islet {beta}-cell proliferation is a very important component of {beta}-cell adaptation to insulin resistance and prevention of type 2 diabetes mellitus. However, we know little about the mechanisms of {beta}-cell proliferation. We now investigate the relationship between pyruvate carboxylase (PC) pathway activity and islet cell proliferation 5 days after 60% pancreatectomy (Px). Islet cell number, protein, and DNA content, indicators of {beta}-cell proliferation, were increased two- to threefold 5 days after Px. PC and pyruvate dehydrogenase (PDH) activities increased only ~1.3-fold; however, islet pyruvate content and malate release from isolated islet mitochondria were approximately threefold increased in Px islets. The latter is an indicator of pyruvate-malate cycle activity, indicating that most of the increased pyruvate was converted to oxaloacetate (OAA) through the PC pathway. The contents of OAA and malate, intermediates of the pyruvate-malate cycle, were also increased threefold. PDH and citrate content were only slightly increased. Importantly, the changes in cell proliferation parameters, glucose utilization, and oxidation and malate release were partially blocked by in vivo treatment with the PC inhibitor phenylacetic acid. Our results suggest that enhanced PC pathway in Px islets may have an important role in islet cell proliferation.

islets of Langerhans; islet cell proliferation; pyruvate-malate cycle; phenylacetic acid


Address for reprint requests and other correspondence: Y. Q. Liu, Kosair Children's Hospital Research Institute, Dept. of Pediatrics, Univ. of Louisville School of Medicine, 570 South Preston St., Suite 304, Louisville, KY 40292 (E-mail: yqliu001{at}gwise.louisville.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.