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Am J Physiol Endocrinol Metab (October 26, 2004). doi:10.1152/ajpendo.00427.2004
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Submitted on September 10, 2004
Accepted on October 24, 2004

Enhanced Rat {beta} Cell Proliferation in 60% Pancreatectomized Islets by Increased Glucose Metabolic Flux through Pyruvate Carboxylase Pathway

Y. Q. Liu1*, J. Han2, P. N. Epstein1, and Y. S. Long2

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

* To whom correspondence should be addressed. E-mail: yqliu001{at}gwise.louisville.edu.

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-day after 60% pancreatectomy (Px). Islet cell number, protein and DNA content, indicators of {beta} cell proliferation, were increased 2-3 folds, 5 days after Px. PC and pyruvate dehydrogenase (PDH) activities increased only about 1.3 folds, however, islet pyruvate content and malate release from isolated islet mitochondria was about 3 folds increased in Px islets. The latter is an indicator of pyruvate-malate cycle activity, indicated that most of the increased pyruvate was converted to oxaloacetate (OAA) through the PC pathway. The content of OAA and malate, intermediates of the pyruvate-malate cycle, were also increased 3 folds. 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.







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