TY - JOUR
T1 - Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states
T2 - Gene structure and 5'-flanking sequence
AU - Argaud, Doriane
AU - Zhang, Qing
AU - Pan, Wansong
AU - Maitra, Subir
AU - Pilkis, Simon J.
AU - Lange, Alex J
PY - 1996
Y1 - 1996
N2 - The mRNA level of the catalytic subunit of rat liver glucose-6- phosphatase (Glu-6-Pase) was regulated by hormones commensurate with activity changes in vivo. Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both mRNA levels and activities of the enzyme are low in the fed and refed state where insulin levels are elevated. Insulin administration to diabetic rats also decreases levels of mRNA and Glu-6-Pase activity. Insulin at a concentration of 1 nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6-Pase message levels in FAO hepatoma cells. The stimulatory response to glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after hormone addition (respectively 1.6- and 3.3- fold). 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons. The exon-intron structure is completely conserved when compared with the mouse and human genes. A 0.5-kb 3'-untranslated region, which is present in rat and mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here, indicating the possible duplication of either the terminal fifth exon or the entire gene. The promoter region contains a consensus core CCAAT element at position -207 and a TATAAA at position -31. Several possible response elements have been identified in the 5'-flanking region (from a HindIII site at position - 1641). A consensus glucocorticoid response element is located at base pair - 1552, a 9/10 match of the insulin response sequence is located at position - 1449, and a 7/8 match of the cAMP response element is located at position - 164.
AB - The mRNA level of the catalytic subunit of rat liver glucose-6- phosphatase (Glu-6-Pase) was regulated by hormones commensurate with activity changes in vivo. Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both mRNA levels and activities of the enzyme are low in the fed and refed state where insulin levels are elevated. Insulin administration to diabetic rats also decreases levels of mRNA and Glu-6-Pase activity. Insulin at a concentration of 1 nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6-Pase message levels in FAO hepatoma cells. The stimulatory response to glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after hormone addition (respectively 1.6- and 3.3- fold). 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons. The exon-intron structure is completely conserved when compared with the mouse and human genes. A 0.5-kb 3'-untranslated region, which is present in rat and mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here, indicating the possible duplication of either the terminal fifth exon or the entire gene. The promoter region contains a consensus core CCAAT element at position -207 and a TATAAA at position -31. Several possible response elements have been identified in the 5'-flanking region (from a HindIII site at position - 1641). A consensus glucocorticoid response element is located at base pair - 1552, a 9/10 match of the insulin response sequence is located at position - 1449, and a 7/8 match of the cAMP response element is located at position - 164.
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U2 - 10.2337/diab.45.11.1563
DO - 10.2337/diab.45.11.1563
M3 - Article
C2 - 8866562
AN - SCOPUS:0029958181
SN - 0012-1797
VL - 45
SP - 1563
EP - 1571
JO - Diabetes
JF - Diabetes
IS - 11
ER -