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Research Article Free access | 10.1172/JCI113506

In vivo regulation of glycolytic and gluconeogenic enzyme gene expression in newborn rat liver.

S Lyonnet, C Coupé, J Girard, A Kahn, and A Munnich

Institut National de la Santé et de la Recherche Médicale U129, Unité de Génétique et Pathologie Moléculaires, Paris, France.

Find articles by Lyonnet, S. in: PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale U129, Unité de Génétique et Pathologie Moléculaires, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U129, Unité de Génétique et Pathologie Moléculaires, Paris, France.

Find articles by Girard, J. in: PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale U129, Unité de Génétique et Pathologie Moléculaires, Paris, France.

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Institut National de la Santé et de la Recherche Médicale U129, Unité de Génétique et Pathologie Moléculaires, Paris, France.

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Published June 1, 1988 - More info

Published in Volume 81, Issue 6 on June 1, 1988
J Clin Invest. 1988;81(6):1682–1689. https://doi.org/10.1172/JCI113506.
© 1988 The American Society for Clinical Investigation
Published June 1, 1988 - Version history
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Abstract

Glucagon and its second messenger, cAMP, are known to rapidly block expression of the L-type pyruvate kinase gene and to stimulate expression of phosphoenolpyruvate (PEP) carboxykinase gene in the liver in vivo. The respective roles, however, of hyperglucagonemia, insulinopenia, and carbohydrate deprivation in the inhibition of L-type pyruvate kinase gene expression during fasting are poorly understood. In addition, the long-term effects of physiological hyperglucagonemia on expression of the two genes are not known. In this study, we investigate the effects of long-term physiological hyperglucagonemia and insulinopenia induced by suckling (which provides a high-fat, low-carbohydrate diet) on expression of the two genes in the liver of normal newborn rats. We show that transcription of the L-type pyruvate kinase gene is inhibited at birth and remains low during the whole suckling period, whereas transcription of the PEP carboxykinase gene is maximal in the neonate, and then decreases despite very high levels of plasma glucagon during suckling. In contrast to the adult, however, in which L-type pyruvate kinase gene expression in the liver is blocked by cAMP and stimulated by carbohydrates, the regulation of L-type pyruvate kinase gene expression in the newborn undergoes a developmental maturation: the inhibitory effect of glucagon is never complete in developing rat liver and the stimulatory effect of glucose could not be detected during suckling, due to either hyperglucagonemia, immaturity of the gene regulatory system, or both.

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