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Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene
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Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene
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Journal Article
Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene
1999
Overview
Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene.
D H Ebert ,
L J Bischof ,
R S Streeper ,
S C Chapman ,
C A Svitek ,
J K Goldman ,
C E Mathews ,
E H Leiter ,
J C Hutton and
R M O'Brien
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232-0615,
USA.
Abstract
In liver and kidney, the terminal step in the gluconeogenic pathway is catalyzed by glucose-6-phosphatase (G-6-Pase). This
enzyme is actually a multicomponent system, the catalytic subunit of which was recently cloned. Numerous reports have also
described the presence of G-6-Pase activity in islets, although the role of G-6-Pase in this tissue is unclear. Arden and
associates have described the cloning of a novel cDNA that encodes an islet-specific G-6-Pase catalytic subunit-related protein
(IGRP) (Arden SD, Zahn T, Steegers S, Webb S, Bergman B, O'Brien RM, Hutton JC: Molecular cloning of a pancreatic islet-specific
glucose-6-phosphatase catalytic subunit related protein (IGRP). Diabetes 48:531-542, 1999). We screened a mouse BAC library
with this cDNA to isolate the IGRP gene, which spans approximately 8 kbp of genomic DNA. The exon/intron structure of the
IGRP gene has been mapped and, as with the gene encoding the liver/kidney G-6-Pase catalytic subunit, it is composed of five
exons. The sizes of these exons are 254 (I), 110 (II), 112 (III), 116 (IV), and 1284 (V) bp, similar to those of the G-6-Pase
catalytic subunit gene. Two interspecific backcross DNA mapping panels were used to unambiguously localize the IGRP gene (map
symbol G6pc-rs) to the proximal portion of mouse chromosome 2. The IGRP gene transcription start site was mapped by primer
extension analysis, and the activity of the IGRP gene promoter was analyzed in both the islet-derived HIT cell line and the
liver-derived HepG2 cell line. The IGRP and G-6-Pase catalytic subunit gene promoters show a reciprocal pattern of activity,
with the IGRP promoter being approximately 150-fold more active than the G-6-Pase promoter in HIT cells.
Publisher
American Diabetes Association
Subject
/ Biological and medical sciences
/ Exons
/ Fundamental and applied biological sciences. Psychology
/ Glucose-6-Phosphatase - genetics
/ Humans
/ Introns
/ Islets of Langerhans - metabolism
/ Mice
/ Molecular and cellular biology
/ Sequence Homology, Nucleic Acid
/ Transcription. Transcription factor. Splicing. Rna processing
