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Cell Proliferation in 60% Pancreatectomized Islets by Increased Glucose Metabolic Flux through Pyruvate Carboxylase Pathway
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
cell proliferation is a very important component of
cell adaptation to insulin resistance and prevention of type 2
diabetes mellitus. However, we know little about the mechanisms of
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
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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