Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells

Abstract

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone and dibutyryl cAMP in H4IIE hepatoma cells. A cis-active element located between nucleotides -161 and -152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expression and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus sequence for a cAMP response element. An antibody against the cAMP response element-binding protein caused a supershift in gel-electrophoretic-mobility-shift assays using an oligonucleotide probe representing the glucose 6-phosphatase gene promoter from nucleotides -161 to -152. These results strongly indicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the regulation of transcription of the glucose 6-phosphatase gene by both cAMP and glucocorticoids.

The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions

“…The ⌬Ϫ211/Ϫ187 construct lost the 3Ј-flanking sequence of the HNF-1 site, which may have caused reduced responsiveness. The deletions of the remaining three constructs with reduced or absent glucose responsiveness (⌬Ϫ186/Ϫ162, ⌬Ϫ161/Ϫ137, and ⌬Ϫ136/Ϫ112) remove sequences that, in the homologous regions of the mouse and human G-6-Pase gene promoters, are important cis-regulatory sequences such as insulin-responsive sequences, CREs, and glucocorticoid response elements (7,25,26,40,46,52). Especially intriguing was that the Ϫ186/Ϫ162 deletion cuts through an upstream CRE at Ϫ165/Ϫ158 (termed CRE1 in Ref.…”

Isolation and structural characterization of 2R, 3R taxifolin 3-O-rhamnoside from ethyl acetate extract of Hydnocarpus alpina and its hypoglycemic effect by attenuating hepatic key enzymes of glucose metabolism in streptozotocin-induced diabetic rats

“…Hepatic glucose production is increased in a diabetic state and has been found to be directly associated with the impaired suppression of G6P and FBPase. The activity of G6P is stimulated by cAMP [59] and inhibited via insulin [60]. It has been established that G6P and FBPase activity impairs hepatic glucose utilization, while at the same time enhancing hepatic glucose production.…”

Mechanisms of transcriptional control of glucose metabolism in hepatocytes

“…Этот транскрипционный фактор активен в ши-роком спектре тканей в периоды голодания [33]. Участками связывания CREB являются последователь-ности CRE (cAMP response element), присутствующие в промоторах генов ключевых ферментов глюконео-генеза: глюкозо-6-фосфатазы, пируваткарбоксилазы и ФЕП-карбоксикиназы [34,35].…”