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1 Division of Gastroenterology, Brigham & Women's Hospital, Boston, Massachusetts 02115; 2 Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22901; and 3 Section of Digestive and Liver Diseases, University of Illinois at Chicago College of Medicine and Chicago Veterans Affairs Medical Center-Westside Division, Chicago, Illinois 60612-7323
Gluconeogenesis and glycogenolysis are essential
hepatic functions required for glucose homeostasis. During the initial
phase of hepatic regeneration, the immediate-early genes (IEG) are
rapidly expressed, and the IEG RL-1 encodes for
glucose-6-phosphatase (G-6-Pase).
G-6-Pase is a microsomal enzyme
essential for gluconeogenesis and glycogenolysis. This study employs a
partial-hepatectomy model to examine the expression and activity of
G-6-Pase. After partial hepatectomy,
rat hepatic G-6-Pase gene expression
is transcriptionally regulated, and mRNA levels are increased
30-fold. However, in contrast to this rapid gene induction,
microsomal enzyme activity is unchanged after partial hepatectomy.
Western blotting demonstrates that microsomal
G-6-Pase protein expression is also
unchanged after partial hepatectomy, and similar results are also noted in whole liver homogenate. Thus, despite marked induction in gene expression of the IEG G-6-Pase after
partial hepatectomy, protein expression and enzyme activity remain
unchanged. These data indicate that, although this hepatocyte IEG is
transcriptionally regulated, the physiologically important level of
regulation is posttranscriptional. This highlights the importance of
correlating gene expression of IEG with protein expression and
physiological function.
hepatectomy; glucose homeostasis; immediate-early genes
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